Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Seminars in Cell & Developmental Biology 19 (2008) 71–81 Review Eye evolution: Lens and cornea as an upgrade of animal visual system Kristyna Jonasova, Zbynek Kozmik ∗ Department of Transcriptional Regulation, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, CZ-14220, Prague 4, Czech Republic Available online 13 October 2007 Abstract Lens-containing eyes are a feature of surprisingly broad spectrum of organisms across the animal kingdom that represent a significant improvement of simple eye composed of just photoreceptor cells and pigment cells. It is apparent that such an upgrade of animal visual system has originated numerous times during evolution since many distinct strategies to enhance light refraction through the use of lens and cornea have been utilized. In addition to having an ancient role in prototypical eye formation Pax transcription factors were convergently recruited for regulation of structurally diverse crystallins and genes affecting morphogenesis of various lens-containing eyes. © 2007 Elsevier Ltd. All rights reserved. Keywords: Eye; Lens; Cornea; Evolution; Crystallin Contents 1. 2. 3. 4. 5. 6. Lens and cornea: introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Environmental constraints affecting lens and cornea properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Molecular basis of lens and cornea mediated vision: recruitment of crystallins by a gene sharing strategy . . . . . . . . . . . . . . . . . . . . . . . . . . Transcriptional control of lens crystallin genes: convergent evolution of Pax regulatory sequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Building up the lens: a tale of endless diversity and multiple origins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Summary: implication of lens and cornea upgrade for eye evolutionary history . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Lens and cornea: introduction Vision is one of the most important animal senses. Eyes of some sort occur in many animal phyla (Fig. 1), but their anatomy, ontogenetic origin and degree of sophistication vary enormously [1]. The minimal setting for an eye involves a single photoreceptor in the vicinity of a cell expressing dark shielding pigment [2] situation found, for example, in Hesse eye cups of amphioxus [3]. Primitive eyes can only provide information about light intensity and direction. Adding an optical system such as lens and cornea that could increase light collection and produce an image would dramatically improve optical performance. Lenscontaining (camera-type) eyes can simply be defined as those ∗ Corresponding author. Tel.: +420 2 241062110; fax: +420 2 241063125. E-mail addresses: [email protected] (K. Jonasova), [email protected] (Z. Kozmik). 1084-9521/$ – see front matter © 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.semcdb.2007.10.005 71 72 73 74 74 78 79 79 with an additional refractive element in front of the photoreceptive layer. The cornea is a transparent layer on the eye periphery (usually of a convex shape). The cornea can be represented by a single cell layer (e.g., box jellyfish) but it can also form a complex multilayer organ (e.g., vertebrates). Sometimes it is difficult to distinguish between lens and cornea which function in similar ways. Eyes where cornea and lens are united as a single unit (e.g., corneal lens in Drosophila ommatidium) are known as well as eyes where the cornea has all (e.g., terrestrial vertebrates) or almost no (e.g., underwater animals) refractive power. Apart from its refractive function, a cornea can serve as protection for the eye, a nutritive device or a light filter [4–6]. The complex of the cornea and lens is known as a refracton [7]. This review aims to discuss evolution of lens-containing eyes using a combination of morphological, ontogenetic, optical and molecular data. We have chosen six model organisms representing distantly related animals (box jellyfish, fruit fly, scallop, 72 K. Jonasova, Z. Kozmik / Seminars in Cell & Developmental Biology 19 (2008) 71–81 Fig. 1. Re-occurrence of lens-containing eyes throughout the animal kingdom. A diagram of main animal phyla indicating the presence of lens-containing eyes or eyes without a lens (in the adult or in the larval stage) within each phylum. An eye is defined here as an organ of spatial vision with a minimum requirement of a single pigment cell and at least one photoreceptor cell [2]. The representatives with lens-containing eyes in each phylum are shown in Table 1. squid, zebrafish and mouse) to illustrate different visual strategies. Finally we propose diverse roles of Pax transcription factors in assembly of prototypical eye and in convergent evolution of lens-containing eyes. 2. Environmental constraints affecting lens and cornea properties Whereas primitive eyes can serve as simple dark/light sensors, sophisticated lens-containing eyes are often able to produce a sharp image in the desired plane of focus due to light refraction. Refraction occurs when light rays travel from a medium with a given refractive index to a medium with another. Therefore, the optical characteristics of the eye are primarily determined by whether it is used in air or water (or both) [8]. Terrestrial animals use the refractive power of both cornea and lens because two interfaces air/cornea and ocular fluid/lens have refractive indexes sufficiently different to cause relevant refraction. The aquatic animals mostly use the refractive power of the lens. Almost no refraction takes place on the water/cornea boundary because they have usually very similar refractive indexes [1]. The secret to increasing lens efficiency and thereby compensating for the missing function of the cornea in aquatic species is the small radius of the lens curvature. The spherical shape of the lens makes it possible to shorten the focal length and maintain an appropriate size of the eye. Unfortunately the spherical shape (as the almost universal solution for underwater animals) introduces image aberrations because the properties of the lens vary sharply between the lens center and periphery and the light rays behave differently. The rays coming through the peripheral parts focus onto a different plane than those coming through the entire lens (spherical aberration) and the rays of different wavelengths will be focused differently as well (chromatic aberration). The preferred solution to spherical aberration is a graded refractive index with the maximum in the lens center and minimum on the lens periphery. The light rays break continuously through the entire lens and a one-step refraction change does K. Jonasova, Z. Kozmik / Seminars in Cell & Developmental Biology 19 (2008) 71–81 not occur [9]. Graded refractive index is achieved by the concentration gradient of proteins within a lens. Some aquatic lens centers contain nearly 100% protein (refractive index 1.55) in contrast to terrestrial animals where the maximum usually is 40% protein. The refractive index decreases towards the lens periphery to a value of 1.35 close to the 1.34, refractive index of sea water [10]. A gradient of protein concentration in lens creates a problem of protein aggregation which can cause light scattering. A recent study of a large family of proteins encoding variants of glutathione S-transferase present in squid lens has provided an interesting example of crystallin evolution to achieve concentration gradient without an apparent aggregation [10]. Terrestrial species must integrate the output of two refractive parts of the eye and for this reason many eye designs emerged during evolution [1]. Although the eyes of terrestrial species often profit from the high efficiency of the cornea, some terrestrial animals have fish-like spherical lenses with a gradient of a refractive index, a strategy which maximizes light gathering and is thus particularly advantageous and common in nocturnal species such as the mouse [11,12]. An unusual example of cornea and lens diversity is found among the fish Anableps anableps [13–15]. This fish, living on the air/water interface has specially optimized eyes where one half (dorsal) is modified for air environment and second (ventral) for submerged movement. The aerial and aquatic sections are divided by a pigmented strip on the cornea and have different attributes. The lens is pyriform with two separate visual axes. Indeed two distinct images emerge on the retina. The corneas of the dorsal and ventral eye are very distinct. The dorsal (aerial) cornea is thicker and flatter and contains more proteins (gelsolin and G-actin). This part has also been shown to be glycogen rich and with thicker collagen fibers. The heavily modified upper part (dorsal) of the cornea has been discussed in the context of desiccation protection (glycogen content) and the increased refractive role (thickness) on air. It has been suggested that the ventral part is ineffective as underwater corneas used to be and that the longer visual axis of the lens together with strong accommodation are crucial for aquatic vision of the Anableps. 3. Molecular basis of lens and cornea mediated vision: recruitment of crystallins by a gene sharing strategy The main optical properties of lens and cornea are transparency and refractive power. Proteins that contribute to these optical properties are collectively called crystallins. Crystallins were initially thought to be highly characteristic for their optical functions in the lens but instead they turned out to be neither specialized nor tissue restricted [16]. Crystallins are best defined as highly abundant, cytoplasmic water-soluble proteins responsible for the optical properties of the lens in both vertebrates and invertebrates. The abundance parameter is arbitrary: the protein must simply be present at a sufficient concentration to affect the refractive properties of the lens in a biologically meaningful way in order to be called a crystallin. Known crystallins are generally globular proteins present in the lens as monomers (such as ␥-crystallins), dimers (some -crystallins) or tetramers (such as 73 ␦-crystallins). Vertebrate ␣-crystallins form even higher order aggregates of variable size with multiple (up to about 50) interacting polypeptides. The crystallins account for up to 90 percent of the dry weight of the lens although their absolute concentrations vary between species and also with spatial location in the lens. Crystallin concentrations are generally higher in aquatic than terrestrial animals and in the center of lens than periphery. In order to avoid spherical aberrations crystallin concentration has to decline smoothly from the center to the periphery of spherical lens to create a gradient in refractive index. Lens transparency is maintained when the lens lacks discontinuities of refractive index greater than half the wavelength of the transmitted light. Large fluctuations in the concentration of closely packed crystallins could cause light scattering and affect the quality of the resulting image. In striking contrast to the universal conservation of opsins as the visual pigments in the photoreceptors, the lens crystallins are diverse proteins that are often taxon-specific, i.e. different proteins function as crystallins in different species [17–19]. The taxon-specificity of crystallins might be a consequence, at least in some cases, of multiple independent origins of eyes and/or lenses during evolution. Thus, while there is phylogenetic inheritance of crystallins, such as for example the ␦-crystallins in birds and reptiles [20], the crystallin composition within the lens generally does not reflect evolutionary relationships. The diversity and taxon-specificity of lens crystallins throughout the animal kingdom is indicative of convergent evolution of crystallin roles. Certain proteins are preferentially recruited as lens crystallins. Proteins used as lens crystallins are often related or identical to ubiquitously expressed metabolic enzymes or physiological stress proteins. All vertebrate lenses contain the ␣-crystallins belonging to the family of small heat shock proteins [21,22] and the /␥-crystallins that are related to microbial stress proteins [23,24]. Vertebrate ␣-crystallins are effective chaperones that protect partially denatured proteins from aggregating in the lens [25], thus helping to maintain the transparency. The co-option of a protein with chaperone-like activity as a lens crystallin makes sense in light of the lack of protein turnover in vertebrate lenses. Vertebrate lens continues to increase in diameter throughout life. As the lens grows the lens fiber cells differentiate, lose their nuclei and other organelles and are, therefore, incapable of replacing the aging crystallins. As a result, the core of the lens contains proteins produced well before birth that have to last a lifetime. The selective advantage of recruiting enzyme-crystallins is less clear [16]. First, they do not fall within a common metabolic category. The catalytic activities include but are not limited to lactate dehydrogenase (-crystallin), argininosuccinate lyase (␦-crystallin), ␣-enolase (-crystallin) or glyceraldehyde 3-phosphate dehydrogenase (crystallin). Furthermore, some enzyme-crystallins have lost their catalytic activity (e.g. aldehyde dehydrogenase/scallop -crystallin) suggesting that, unless they have gained a new substrate specificity, their function in lens is limited to the structural (refractive) role. An interesting group of enzyme-crystallins with additional putative non-refractive function represent proteins that bind nicotinamide adenine dinucleotide cofactors (NADbinding enzyme-crystallins). It was proposed that NAD-binding 74 K. Jonasova, Z. Kozmik / Seminars in Cell & Developmental Biology 19 (2008) 71–81 enzyme-crystallins present in high amount in lenses could serve as UV filters to reduce glare and/or to protect against oxidative stress [26]. It is possible that NAD-binding contributed to frequent recruitment of this group of enzymes as lens crystallins. There is an intriguing parallel between lens crystallins and abundant, taxon-specific corneal proteins (e.g. aldehyde dehydrogenase). Although their optical (refractive) function has not yet been established the close proximity and co-evolution of lens and cornea, currently viewed as a single unit, the “refracton”, suggest that these abundant proteins might be considered corneal crystallins [7]. An important general concept, ‘gene sharing’, has emerged from crystallin studies [16,19,27]. Gene sharing proposes multiple uses of a single protein encoded in one gene. Thus, the protein encoded by a single gene may perform two entirely different functions: a refractive function in the lens as a lens crystallin and a catalytic or stress function elsewhere (as well as in the lens). An important implication of gene sharing nicely illustrated by the example of lens crystallins is that a protein can evolve a new role, without losing its original function, simply by a change in gene expression [28]. Furthermore the new function is established in the absence of gene duplication [29]. It has become apparent over time that gene sharing and repeated use of proteins for new tasks in general represents a common evolutionary strategy [16]. 4. Transcriptional control of lens crystallin genes: convergent evolution of Pax regulatory sequences Crystallin protein levels in the lens can be affected by multiple parameters such as transcriptional rate, translational efficiency, mRNA or protein stability. However, it appears that the tissuespecific transcriptional regulation plays a key role in recruiting a gene to become crystallin gene. Remarkably, the high lenspreferred expression of non-homologous crystallin genes is regulated by a similar set of transcription factors in vertebrates and invertebrates [30–33]. Many of these transcription factors are either known regulators of lens (or eye) development (e.g. Pax, Sox, Maf, Prox1) or transcription factors sensing oxidative stress (e.g. AP1, CREB) [33]. Perhaps the most remarkable is the widespread conservation of Pax transcription factors as regulators of eye development and crystallin gene expression (reviewed in [34–38]). Molecular dissection of crystallin promoters and enhancers identified a number of functional Pax regulatory elements. First of all, Pax6 can activate or repress many vertebrate crystallin reporter genes in transfection assays. This appears to be a direct effect since many Pax6 binding sites were identified in crystallin regulatory regions by either in vitro or in vivo (chromatin immunoprecipitation) appproaches. In vertebrates, Pax6 has been implicated in regulation of chicken and mouse ␣A-crystallin [39–41] mouse ␣B-crystallin [42], B1-crystallin [43], chicken ␦1-crystallin [44,45], mouse ␥E/␥F-crystallins [46,47] and taxon-specific guinea pig -crystallin [48]. Much less is known about Pax6-mediated crystallin gene regulation in invertebrates. The promoter of the scallop -crystallin gene has an arrangement of putative cis-control elements, including func- tional Pax6 binding sites, surprisingly similar to that used for lens promoter activity of the unrelated ␣A-crystallin genes [31]. Cnidarians who lack a true Pax6 gene [32] have recruited another member of Pax gene family, designated PaxB, for crystallin activation. PaxB corresponds to an ancestral Pax gene encoding a paired domain, homeodomain and an octapeptide [49]. The presence of two independent DNA-binding domains is shared by Pax6 and PaxB. However, specific amino acid changes within paired domain are responsible for their distinct DNA-binding specificities. In box jellyfish Tripedalia cystophora possessing well-developed lens-containing eyes PaxB binding sites were identified in J-crystallin promoters. Furthermore, PaxB binding sites appeared functional as judged by site-specific mutagenesis and transfection tests ([32]; Kozmik et al., submitted). The data indicate that modern Pax2 and Pax6 genes evolved from PaxB ancestor by duplication and diversification in higher metazoans. Thus the structurally similar yet functionally distinct members of Pax gene family were recruited to achieve lens-specific crystallin expression in diverse phyla. It is interesting to note that in all known cases of Pax-mediated crystallin regulation it is the paired domain and not the homeodomain, which mediates the effect. This situation is reminiscent of the role of individual domains in general morphogenesis of animal eyes. At least on the basis of genetic data in vertebrates and flies, the Pax6 paired domain seems to be more important than is the homeodomain for eye morphogenesis [50,51]. The presence of similar cis-acting elements for a common set of transcription factors, especially Pax, in non-homologous crystallin genes in various animal species is due to convergent evolution. It reflects the situation that the diverse crystallin genes have been recruited independently during evolution and hence their regulatory elements to achieve lens-preferred expression must have been acquired by independent events as well. 5. Building up the lens: a tale of endless diversity and multiple origins The level of sophistication of animal eyes is generally not correlated with the complexity of animal body plan. Lens-containing eyes representing a significant improvement of visual system are sprinkled throughout the animal kingdom (Fig. 1, Table 1). The first metazoan eyes with lens are found in the basal phylum Cnidaria. Two out of seven main ecdysozoan’s phyla developed an eye with a lens. Onychophorans (velvet worms) possess paired eyes with secreted cuticular cornea and secreted acellular lens from granular material, with the whole eye being of epidermal origin [52]. The huge phylum of arthropods includes mainly species with compound eyes (either sessile or stalked) or single-chambered eyes with corneal lens. The lophotrochozoan group includes large phyla such as mollusks, annelids and plathelminthes. Mollusks are characterized by unusual diversity of their visual system including sophisticated camera-type (squid) or mirror-containing eyes (scallop). Within the annelid phylum there are representatives with lens eyes among polychaetes. A simple cup eye, K. Jonasova, Z. Kozmik / Seminars in Cell & Developmental Biology 19 (2008) 71–81 75 Table 1 A table comprising those phyla where lens-containing eye occurs Phylum Representative Lens type Reference Cnidaria Hydrozoa Cubozoa Onychophorans Cladonema radiatum Tripedalia cystophora Perpatonder novaezealandiae Lens bodies Cellular lens Non-cellular lens [101] [65] [52] Porcelio scaber Portia fimbriata Craterostigmus tasmanianus Drosophila melanogaster Entobdella soleae Corneal lens and crystalline cone Corneal lens and secondary retinal lens Corneal lens Corneal lens and crystalline cone Mitochondrial lens Odontosyllis enopla Cellular lens [102] [103] [104] [105] (lens secretion) [56] [55] [53] Hermissenda crassicornis Pecten maximus Loligo opalescens Ophiocoma wendtii Ciona intestinalis Anableps anableps Non-cellular lens (secreted) Cellular lens Non-cellular lens (fused procceses) Calcitic lens Three-cell lens Cellular lens [107] [69] [73] [58] [106] [13] Arthropods Crustaceans Cheliceriformes Myriapoda Hexapoda Plathelminthes Nemerteans Annelids Mollusks Gastropoda Bivalvia Cephalopoda Echinoderms Tunicates Craniates For each phylum at least one representative with lens type specification and reference is given. a lensed cup eye (nereid, platynereis) as well as complex eyes with spherical lens (Vanadis, Odontosyllis) occur in this diverse class [53–55]. Really peculiar lenses with a likely mitochondrial origin have been identified within the phylum Plathelminthes [56,57]. Proteins are not the only refractive material used for a lens as exemplified by the echinoderm phylum. Some brittlestars use a unique system of vision based on calcitic lenses [58]. Similar calcitic lenses have been discovered also within trilobite fossils [59]. The origin of vertebrate lens is probably the most interesting question in relation to our own vision. When we follow the proposed vertebrate line – cephalochordates (amphioxus)–tunicates (ciona)–craniata/hyperotreti (hagfish)–vertebrates/hyperoartia (lamprey)–vertebrates/chondrichtyes (shark)–vertebrates/teleostomi (fish) – it is possible to see the development of the concept of lens. It is thought that the image-forming eye of vertebrates evolved after cephalochordates split [3]. Based on the fossil record of early chordates, such as pikaya, it appears that those animals did not have prominent paired eyes. A frontal eye of the amphioxus with ciliated photoreceptor cells therefore most likely represents an ancestral condition from which paired bilateral eyes of vertebrates formed rather than a derived (regressed) state. Already in tunicates which were shown to be closer to vertebrates than cephalochordates [60], there is an ocellus with three-cell lens in the larval stage of some species. Study of Ciona ␥-crystallin suggests that chordate ␥-crystallin ancestor was already expressed in a cell-specific manner in derivatives of a primitive visual system prior to the evolution of the lens in vertebrate lineage [61]. Hagfish have a poorly developed visual system (probably as a result of regression) in contrast to lampreys that previously had relatively small but fish-like eyes with almost spherical multicellular lens covered closely with a thin cornea [62]. And finally, the spherical lens with appropriate gradient of refractive index is the best solution for aquatic animal; consequently this design is usually maintained among fishes, the true vertebrates [9]. Diversity of lens-containing eyes is observed at every level of comparison–structural design, ontogenetic origin or the crystallin content. Yet the final morphological appearance of lens-containing eyes is often remarkably similar suggesting independent origins by convergent evolution. In the following paragraphs we compare and contrast eyes of six organisms representing distantly related animals (box jellyfish, fruit fly, scallop, squid, zebrafish and mouse) to illustrate different visual strategies (Fig. 2). In box jellyfish (Tripedalia cystophora) very complex structures characteristic of more advanced animals appear such as the camera-type eye situated within four sensory organs called rhopalia. Each rhopalium carries six eyes: two pit-shaped, two slit-shaped and two complex with a cellular lens. The eyes with lens are covered with a thin cornea, but differ in size, lens shape, retinal geometry, as well as in gradient of a refractive index [63]. The cornea is de facto a part of a single layer covering the entire rhopalium and has no refractive capacity. The large biconvex lens has a homogenous center and a peripheral gradient but the drop-shaped lens of the small eye has an almost perfect gradient through the lens correcting its aberrations. The resulting image produced by the lenses is severely out of focus and, i.e., blurred. It can be functional as a low-pass filter for this animal which would not be able to use a more complex image [63]. The rhopalium develops during metamorphosis of the polyp into the medusa stage from a dedifferentiated cell derived from fused polyp tentacles and thus the lenses are originally derived from myoepithelial cells [64]. None of the Tripedalia crystallins have a sequence relationship to other crystallins in any other species [65–68]. Two crystallins, J1 and J2, provide a majority of crystallins within the lens of both the small and large eye. 76 K. Jonasova, Z. Kozmik / Seminars in Cell & Developmental Biology 19 (2008) 71–81 Fig. 2. Lens-containing eyes of selected model organisms. (A) Phylogenetic distances of selected model organisms and their distribution across the animal kingdom. Splits between clades are indicated in million years (mya). (B) Hematoxylin-eosin stained sections of animal eyes showing differences in lens and cornea shape and structure. Note the crystalline core of the fish lens (medaka) and an unusual shape of scallop’s lens. L, lens; c, cornea. (C) A schematic diagram illustrating the eye morphology, crystallin variability and refractive index (n) in the center of the lens of selected model animals [84,63,69,10,100]. K. Jonasova, Z. Kozmik / Seminars in Cell & Developmental Biology 19 (2008) 71–81 The lens in the scallop (Argopecten irradians) eye, unlike other underwater animals, has a homogenous refractive index and a hemispheric shape [69]. This is because the image is produced by the mirror on the posterior wall of the eye but not by the lens. The mirror formed by the layer called argentea or tapetum consists of layers of guanine crystals and has a refractive index of 1.8 [69]. Light rays coming through the lens reflect on the distal retina neighboring the mirror. The lens probably has a role in correcting the spherical aberration of the mirror. Lens of the bay scallop was described as soft (in contrast to fish) and filled with one major crystallin (-crystallin) identified as an aldehyde dehydrogenase and noted ALDH1A9 [31]. The cooption of an ALDH enzyme as a crystallin has occurred several times in vertebrates or in invertebrates. Scallop -crystallin has homology to squid and an octopus minor lens -crystallin [70]. -crystallins are enzymatically inactive. It is also expressed in the cornea and together with other records of corneal crystallin expression supports the idea of its role as a corneal crystallin [71]. A squid (Loligo opalescens) possesses an eye with a spherical lens that has a graded refractive index compensating for spherical and other aberrations [72]. A cephalopod lens differs markedly in development compared to vertebrates (although the resulting lens design of fish and squid is very similar). Vertebrate lenses develop by invagination or delamination of the surface ectoderm. The squid lens originates also from the ectoderm but from two distinguishable parts. Each part is a primordium of one of the two future halves of the lens. Lentigenic cells of the anterior and posterior primordium give rise to a bipartite lens which is derived from ectodermal cellular processes and thus does not have a completely cellular state. The posterior lens primordium arises as the first and later the anterior forms a smaller plate-like element of the lens which is thickened during development. The two parts of the lens are separated by septum, a thin layer of living cells [73,74]. In addition, the cornea is derived from epithelial tissue. This tissue from the posterior part of the eye is probably moved by neighboring muscle cell contractions and migrates over the eyeball [75]. Modified glutathione S-transferase is a major crystallin (S-crystallin) of the squid ocular lens [76] but aldehyde dehydrogenase has also been identified as a minor crystallin (crystallin). This enzyme has been further recruited for the lens of the light organ where it was denoted as L-crystallin [77]. Of special interest is the fact that there are more than 25 isoforms of the S-crystallin in the ocular lens of the squid that are differentially expressed to maintain optical performance and clarity of lens [10]. It has been suggested that gene duplications followed by mutations to accumulate positive charge in S-crystallin were essential to achieve concentration gradient without an apparent aggregation [10]. The compound eye of the fruit fly (Drosophila melanogaster) consists of hundreds of ommatidia which are composed of two main refractive parts: corneal lens secreted by underlying corneagen cells and a four-part crystalline cone (pseudocone) produced by cone (Semper) cells. The receptive part under the corneal lens and cones consists of photoreceptors (rhabdomeres) with rhabdoms. In addition to the refractive and receptive parts are pigment cells which restrain the receptive field and separate 77 ommatidia. The compound eye originates during metamorphosis from a simple epithelium of the eye disc involving highly complex pattern-creating events. The corneal lens as well as cones are epithelial derivatives (secreted by cone cells, corneagen cells and primary pigment cells) and serve as independent surfaces for multiple refraction [1,55]. A 52 kDa large glycoprotein (known as drosocrystallin) has been described as a major protein of the corneal lens [78]. It was shown that drosocrystallin is a homologue of a cuticle protein indicating that a gene-sharing strategy has been used in arthropods. The eyes of zebrafish (Danio rerio) are laterally placed and the protuberant lenses allow for panoramic vision. A zebrafish lens is spherical having a refractive index gradient with the maximum refractive index in the center of the lens. The whole eye is developed within first 3 days after fertilization but growth continues for 1 month [79,80]. The development is similar to that of other vertebrates but important differences have been found. The lens does not originate from the surface ectoderm by the process of invagination as known for other vertebrates but a thickened lens placode undergoes delamination. Thus the lens vesicle rises as a compact formation and primary fiber cells are formed from the central cell cluster (and not from posterior epithelial cells) forming the nucleus of the lens. Three classes of crystallins (␣-, -, ␥-) typical for vertebrates are expressed in zebrafish lens. Among those more than sixteen ␥-crystallins have been found including nine ␥M-crystallins characteristic for aquatic animals and two ␥N-crystallins which were described as evolutionary hybrids of - and ␥-crystallins [81]. Corneal crystallins of the gelsolin protein family have been described for zebrafish [82]. It is a diverged paralogue of the vertebrate scinderin gene with calcium- and actin-binding and actin-severing capabilities. Six genes have been cloned and sequenced, three of them with preferential expression in the cornea [83]. Gelsolin-like proteins were found in zebrafish as well as in Anableps where the expression varies between ventral and dorsal cornea [14,83]. The nocturnal mouse (Mus musculus) has a large spherical lens and curved cornea that are ideal for very short focal length and maximal light gathering capacity [1,84]. Both cornea and lens function in light focusing in mouse. A critical region of cornea for refraction is collagen rich stroma where collagen fiber bundles form a highly ordered three-dimensional network [85,86]. The lens has an almost spherical shape that suffers from spherical aberrations and has a smooth gradient of refractive index [87]. Taken together, mouse is able to gather much more light than the human eye can, but the quality of the image is decidedly worse [87]. Mouse lens arises by invagination of surface ectoderm for which the interaction with optic vesicle (neural ectoderm) is a key inductive step (for review see [88]). The corneal epithelium develops at first from anterior surface ectoderm. Migrating periocular mesenchymal cells (neural crest and paraxial mesoderm cells) give rise to presumptive corneal stroma. The posterior part of the cornea differentiates later into corneal endothelium. As in zebrafish, all three major vertebrate crystallin classes (␣-, -, ␥-) are present in the mouse lens. ␣Acrystallin is expressed mainly in the lens while ␣B-crystallin is an ubiquitous protein. The elimination of ␣A-crystallin in mice leads smaller and opaque lenses [89] while ␣B-crystallin- 78 K. Jonasova, Z. Kozmik / Seminars in Cell & Developmental Biology 19 (2008) 71–81 defficient mice exhibit more pleiotropic phenotypes associated primarily with muscles and heart [90,91]. A cluster of six ␥-crystallins (A–F) typical for placental mammals is expressed within the mouse lens [92]. The main corneal crystallin in mouse is ALDH3a1 [93,94]. Interestingly, although ALDH3a1 comprises nearly one-half of the water-soluble protein fraction in the corneal epithelium, the ALDH3a1 knockout mouse contains no detectable defects in corneal morphology or transparency [95]. 6. Summary: implication of lens and cornea upgrade for eye evolutionary history The eye has challenged generations of evolutionary biologists. Whether an eye originated once (monophyletic origin) or multiple times (polyphyletic origin) still remains a controversial topic. Despite obvious anatomical, developmental and organizational differences between mouse and Drosophila eyes, genetic studies have indicated that a homologous gene, Pax6, directs development of eyes in both species [96,97]. Since then more evidence has emerged for an almost universal re-deployment of Pax genes for animal eye development [32,34]. Such common underlying genetic mechanism provides a powerful argument for monophyletic eye origin [34] and might reflect an ancient role of Pax genes in functioning of a “primitive eye” (eye prototype) composed of a photoreceptor cell and a shielding pigment cell. A bipartite model proposes that the two independent DNA binding domains within a single Pax transcription factor have been co-opted for two essential features of the prototypical eye [35] (Fig. 3, top). Production of a dark shielding pigment (‘pigmentation’ program) has been controlled by paired domain and production of a photopigment (‘opsin’ program) by homeodomain. Once such transcriptional regulatory network was established the two genetic programs being driven by two independent DNA binding domains within a single transcription factor became virtually inseparable. In contrast, the enormous morphological diversity found among animal eyes seems incompatible with monophyletic Fig. 3. Diverse roles of Pax transcription factors during eye evolution. All eyes require an assembly of photoreceptor cells (grey) and shielding pigment cells (black). An almost universal use of Pax genes in eye formation throughout the animal kingdom argues for their ancient role in generation of a prototypical eye as a photoreceptor/pigment cell combination (top). The bipartite ‘Paxcentric model’ [35] proposed independent functions of paired domain and homeodomain of Pax transcription factors in regulating either photoreceptor or pigment cell programs. Lens-containing eyes have evolved independently multiple times. Pax transcription factors are likely involved in the divergent morphogenesis of various types of lens-containing eyes. Convergent evolution of Pax regulatory elements was a driving force behind the recruitment of lens crystallin genes and eye ‘morphogenesis’ genes. ‘Morphogenesis’ genes are the ones required for eye development in any given animal. Note that opsin genes are homologous across phylogeny, whereas lens crystallins are encoded by structurally unrelated genes in different species. K. Jonasova, Z. Kozmik / Seminars in Cell & Developmental Biology 19 (2008) 71–81 origin but is rather consistent with convergent evolution and multiple independent origins [98]. Theoretical modeling suggested that a camera-type eye can evolve from a flat layer of photosensitive epithelium in less than 400,000 generations [99]. We can view camera-type (lens-containing) eyes as a significant improvement of primitive eyes that has allowed animals to gather more light onto their photoreceptors and to obtain a focused image. Such an upgrade of eyes by addition of a lens (and cornea) was a milestone during eye evolution. As described above amazingly broad and distinct strategies of how to design lens and cornea have been utilized by different animals. It follows that the lens/cornea upgrade of animal eyes has a polyphyletic origin. It is almost impossible to find anything uniting corneal lens of jumping spiders and spherical lens of fish. There is no doubt that even in the case of cellular lenses with their crucial refractive ability provided by an accumulation of crystallins it is safe to argue for multiple independent origins because the genes encoding lens (and corneal) crystallins are almost always taxon-specific [16]. It is intriguing that the same transcription factors, especially Pax, were used once again as key regulators in lens/cornea upgrade. Pax regulatory elements were essential for convergent recruitment of lens and corneal crystallins as well as for driving the divergent morphogenesis of various types of lens-containing eyes (Fig. 3, bottom). In summary, animal eyes have evolved by convergent mechanisms a variety of lenses and corneas containing diverse crystallins and displaying multiple differences for achieving their visual functions. Acknowledgements We would like to thank Jana Ruzickova, Roger Hanlon, Marek Jindra for providing some animal photographs. Work in Kozmik’s laboratory is supported by Grant nos. AV0Z50520514 and IAA500520604 from the Academy of Sciences of the Czech Republic and by Center for Applied Genomics grant no. 1M6837805002 awarded by Ministry of Education, Youths and Sports of the Czech Republic. References [1] Land MF, Nilsson DE. Animal eyes. Oxford: Oxford University Press; 2002. [2] Arendt D, Wittbrodt J. Reconstructing the eyes of Urbilateria. Philos Trans R Soc Lond B Biol Sci 2001;356(1414):1545–63. [3] Lacalli TC. Sensory systems in amphioxus: a window on the ancestral chordate condition. Brain Behav Evol 2004;64(3):148–62. [4] Collin HB, Collin SP. The corneal surface of aquatic vertebrates: microstructures with optical and nutritional function? Philos Trans R Soc Lond B Biol Sci 2000;355(1401):1171–6. [5] Heinermann PH. Yellow intraocular filters in fishes. Exp Biol 1984;43(2):127–47. [6] Ringvold A. Corneal epithelium and UV-protection of the eye. Acta Ophthalmol Scand 1998;76(2):149–53. [7] Piatigorsky J. Enigma of the abundant water-soluble cytoplasmic proteins of the cornea: the “refracton” hypothesis. Cornea 2001;20(8):853–8. [8] Sivak JG. Accommodation in vertebrates: a contemporary survey. New York: Academic Press; 1980. [9] Jagger WS. The optics of the spherical fish lens. Vision Res 1992;32(7):1271–84. 79 [10] Sweeney AM, Des Marais DL, Andrew Ban YE, Johnsen S. Evolution of graded refractive index in squid lenses. J R Soc Interface 2007. [11] Kroger RH, Campbell MC, Fernald RD, Wagner HJ. Multifocal lenses compensate for chromatic defocus in vertebrate eyes. J Comp Physiol [A] 1999;184(4):361–9. [12] Malmstrom T, Kroger RH. Pupil shapes and lens optics in the eyes of terrestrial vertebrates. J Exp Biol 2006;209(Pt 1):18–25. [13] Sivak JG. Optics of the eye of the “four-eyed fish” (Anableps anableps). Vision Res 1976;16(5):531–4. [14] Kanungo J, Swamynathan SK, Piatigorsky J. Abundant corneal gelsolin in Zebrafish and the ’four-eyed’ fish. Anableps anableps: possible analogy with multifunctional lens crystallins. Exp Eye Res 2004;79(6):949–56. [15] Swamynathan SK, Crawford MA, Robison Jr WG, Kanungo J, Piatigorsky J. Adaptive differences in the structure and macromolecular compositions of the air and water corneas of the “four-eyed” fish (Anableps anableps). FASEB J 2003;17(14):1996–2005. [16] Piatigorsky J. Gene sharing and evolution: the diversity of protein functions. Cambridge: Harvard University Press; 2007. [17] de Jong WW, Hendriks W, Mulders JW, Bloemendal H. Evolution of eye lens crystallins: the stress connection. Trends Biochem Sci 1989;14(9):365–8. [18] Wistow GJ, Piatigorsky J. Lens crystallins: the evolution and expression of proteins for a highly specialized tissue. Annu Rev Biochem 1988;57:479–504. [19] Piatigorsky J, Wistow GJ. Enzyme/crystallins: gene sharing as an evolutionary strategy. Cell 1989;57(2):197–9. [20] Piatigorsky J. Delta crystallins and their nucleic acids. Mol Cell Biochem 1984;59(1/2):33–56. [21] de Jong WW, Leunissen JA, Voorter CE. Evolution of the alpha-crystallin/small heat-shock protein family. Mol Biol Evol 1993;10(1):103–26. [22] Ingolia TD, Craig EA. Four small Drosophila heat shock proteins are related to each other and to mammalian alpha-crystallin. Proc Natl Acad Sci USA 1982;79(7):2360–4. [23] D’Alessio G. The evolution of monomeric and oligomeric betagamma-type crystallins, facts and hypotheses. Eur J Biochem 2002;269(13):3122–30. [24] Wistow G. Evolution of a protein superfamily: relationships between vertebrate lens crystallins and microorganism dormancy proteins. J Mol Evol 1990;30(2):140–5. [25] Horwitz J. Alpha-crystallin can function as a molecular chaperone. Proc Natl Acad Sci USA 1992;89(21):10449–53. [26] Wistow G, Molecular Biology. Evolution of crystallins: gene recruitment and multifunctional proteins in the eye lens. New York: Springer; 1995. [27] Piatigorsky J, O’Brien WE, Norman BL, Kalumuck K, Wistow GJ, Borras T, et al. Gene sharing by delta-crystallin and argininosuccinate lyase. Proc Natl Acad Sci USA 1988;85(10):3479–83. [28] Piatigorsky J, Wistow G. The recruitment of crystallins: new functions precede gene duplication. Science 1991;252(5010):1078–9. [29] Piatigorsky J. Crystallin genes: specialization by changes in gene regulation may precede gene duplication. J Struct Funct Genomics 2003;3(1–4):131–7. [30] Tomarev SI, Duncan MK, Roth HJ, Cvekl A, Piatigorsky J. Convergent evolution of crystallin gene regulation in squid and chicken: the AP1/ARE connection. J Mol Evol 1994;39(2):134–43. [31] Carosa E, Kozmik Z, Rall JE, Piatigorsky J. Structure and expression of the scallop Omega-crystallin gene. Evidence for convergent evolution of promoter sequences. J Biol Chem 2002;277(1):656–64. [32] Kozmik Z, Daube M, Frei E, Norman B, Kos L, Dishaw LJ, et al. Role of Pax genes in eye evolution: a cnidarian PaxB gene uniting Pax2 and Pax6 functions. Dev Cell 2003;5(5):773–85. [33] Duncan MK, Cvekl A, Kantorow M, Piatigorsky J. Lens crystallins. New York: Cambridge University Press; 2004. [34] Gehring WJ, Ikeo K. Pax 6: mastering eye morphogenesis and eye evolution. Trends Genet 1999;15(9):371–7. [35] Kozmik Z. Pax genes in eye development and evolution. Curr Opin Genet Dev 2005;15(4):430–8. 80 K. Jonasova, Z. Kozmik / Seminars in Cell & Developmental Biology 19 (2008) 71–81 [36] Cvekl A, Piatigorsky J. Lens development and crystallin gene expression: many roles for Pax-6. Bioessays 1996;18(8):621–30. [37] Cvekl A, Yang Y, Chauhan BK, Cveklova K. Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred expression of crystallins in lens. Int J Dev Biol 2004;48(8/9):829–44. [38] Kondoh H, Uchikawa M, Kamachi Y. Interplay of Pax6 and SOX2 in lens development as a paradigm of genetic switch mechanisms for cell differentiation. Int J Dev Biol 2004;48(89):819–27. [39] Cvekl A, Sax CM, Bresnick EH, Piatigorsky J. A complex array of positive and negative elements regulates the chicken alpha A-crystallin gene: involvement of Pax-6, USF, CREB and/or CREM, and AP-1 proteins. Mol Cell Biol 1994;14(11):7363–76. [40] Cvekl A, Kashanchi F, Sax CM, Brady JN, Piatigorsky J. Transcriptional regulation of the mouse alpha A-crystallin gene: activation dependent on a cyclic AMP-responsive element (DE1/CRE) and a Pax-6-binding site. Mol Cell Biol 1995;15(2):653–60. [41] Yang Y, Stopka T, Golestaneh N, Wang Y, Wu K, Li A, et al. Regulation of alphaA-crystallin via Pax6, c-Maf, CREB and a broad domain of lensspecific chromatin. EMBO J 2006;25(10):2107–18. [42] Gopal-Srivastava R, Cvekl A, Piatigorsky J. Pax-6 and alphaBcrystallin/small heat shock protein gene regulation in the murine lens. Interaction with the lens-specific regions, LSR1 and LSR2. J Biol Chem 1996;271(38):23029–36. [43] Duncan MK, Haynes II JI, Cvekl A, Piatigorsky J. Dual roles for Pax-6: a transcriptional repressor of lens fiber cell-specific beta-crystallin genes. Mol Cell Biol 1998;18(9):5579–86. [44] Cvekl A, Sax CM, Li X, McDermott JB, Piatigorsky J. Pax-6 and lensspecific transcription of the chicken delta 1-crystallin gene. Proc Natl Acad Sci USA 1995;92(10):4681–5. [45] Kamachi Y, Uchikawa M, Tanouchi A, Sekido R, Kondoh H. Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development. Genes Dev 2001;15(10):1272–86. [46] Kralova J, Czerny T, Spanielova H, Ratajova V, Kozmik Z. Complex regulatory element within the gammaE- and gammaF-crystallin enhancers mediates Pax6 regulation and is required for induction by retinoic acid. Gene 2002;286(2):271–82. [47] Yang Y, Chauhan BK, Cveklova K, Cvekl A. Transcriptional regulation of mouse alphaB- and gammaF-crystallin genes in lens: opposite promoterspecific interactions between Pax6 and large Maf transcription factors. J Mol Biol 2004;344(2):351–68. [48] Richardson J, Cvekl A, Wistow G. Pax-6 is essential for lensspecific expression of zeta-crystallin. Proc Natl Acad Sci USA 1995;92(10):4676–80. [49] Balczarek KA, Lai ZC, Kumar S. Evolution of functional diversification of the paired box (Pax) DNA-binding domains. Mol Biol Evol 1997;14(8):829–42. [50] Hanson I, Churchill A, Love J, Axton R, Moore T, Clarke M, et al. Missense mutations in the most ancient residues of the PAX6 paired domain underlie a spectrum of human congenital eye malformations. Hum Mol Genet 1999;8(2):165–72. [51] Punzo C, Kurata S, Gehring WJ. The eyeless homeodomain is dispensable for eye development in Drosophila. Genes Dev 2001;15(13):1716–23. [52] Eakin RM, Westfall JA. Fine structure of the eye of peripatus (Onychophora). Z Zellforsch Mikrosk Anat 1965;68(2):278–300. [53] Wolken JJ, Florida RG. The eye structure of the bioluminescent fireworm of Bermuda, Odontosyllis enopla. Biol Bull 1984;166:260–8. [54] Hermans CO, Eakin RM. Fine structure of the eyes of an alciopid polychaete, Vanadis tagensis (Annelida). Zoomorphology 1974;79:245–67. [55] Brusca RC, Brusca GJ.Invertebrates. 2nd ed. Sunderland: Sinauer Associates, Inc.; 2003. [56] Sopott-Ehlers B, Kearn GC, Ehlers U. Evidence for the mitochondrial origin of the eye lenses in embryos of Entobdella soleae (Plathelminthes, Monogenea). Parasitol Res 2001;87(6):421–7. [57] Sopott-Ehlers B, Haas W, Ehlers U. Ultrastructure of pigmented and unpigmented photoreceptors in cercariae of Trichobilharzia ocellata (Plathelminthes, Trematoda, Schistosomatidae): evidence for the evolution of parasitism in Neodermata. Parasitol Res 2003;91(2):109– 16. [58] Aizenberg J, Tkachenko A, Weiner S, Addadi L, Hendler G. Calcitic microlenses as part of the photoreceptor system in brittlestars. Nature 2001;412(6849):819–22. [59] Fortey R, Chatterton B. A Devonian trilobite with an eyeshade. Science 2003;301(5640):1689. [60] Delsuc F, Brinkmann H, Chourrout D, Philippe H. Tunicates and not cephalochordates are the closest living relatives of vertebrates. Nature 2006;439(7079):965–8. [61] Shimeld SM, Purkiss AG, Dirks RP, Bateman OA, Slingsby C, Lubsen NH. Urochordate betagamma-crystallin and the evolutionary origin of the vertebrate eye lens. Curr Biol 2005;15(18):1684–9. [62] Collin SP, Fritzsch B. Observation on the shape of the lens in the eye of the silver lamprey, Ichtyomyzon unicupis. Can J Zool 1992;71:34–41. [63] Nilsson DE, Gislen L, Coates MM, Skogh C, Garm A. Advanced optics in a jellyfish eye. Nature 2005;435(7039):201–5. [64] Laska-Mehnert G. Cytologische Veränderungen während der Metamorphose des Cubopolypen Tripedalia cystophora (Cubozoa, Carybdeidae) in die Medusa. Helgoländer Meeresuntersuchungen 1985;39:129–67. [65] Piatigorsky J, Horwitz J, Kuwabara T, Cutress CE. The cellular eye lens and crystallins of cubomedusan jellyfish. J Comp Physiol [A] 1989;164(5):577–87. [66] Piatigorsky J, Horwitz J, Norman BL. J1-crystallins of the cubomedusan jellyfish lens constitute a novel family encoded in at least three intronless genes. J Biol Chem 1993;268(16):11894–901. [67] Piatigorsky J, Kozmik Z. Cubozoan jellyfish: an Evo/Devo model for eyes and other sensory systems. Int J Dev Biol 2004;48(8/9):719–29. [68] Piatigorsky J, Norman B, Dishaw LJ, Kos L, Horwitz J, Steinbach PJ, et al. J3-crystallin of the jellyfish lens: similarity to saposins. Proc Natl Acad Sci USA 2001;98(22):12362–7. [69] Land MF. Image formation by a concave reflector in the eye of the scallop, Pecten maximus. J Physiol 1965;179(1):138–53. [70] Piatigorsky J, Kozmik Z, Horwitz J, Ding L, Carosa E, Robison Jr WG, et al. Omega-crystallin of the scallop lens. A dimeric aldehyde dehydrogenase class 1/2 enzyme-crystallin. J Biol Chem 2000;275(52):41064–73. [71] Jester JV, Moller-Pedersen T, Huang J, Sax CM, Kays WT, Cavangh HD, et al. The cellular basis of corneal transparency: evidence for ‘corneal crystallins’. J Cell Sci 1999;112(Pt 5):613–22. [72] Jagger WS, Sands PJ. A wide-angle gradient index optical model of the crystalline lens and eye of the octopus. Vision Res 1999;39(17):2841–52. [73] West JA, Sivak JG, Doughty MJ. Microscopical evaluation of the crystalline lens of the squid (Loligo opalescens) during embryonic development. Exp Eye Res 1995;60(1):19–35. [74] Sivak JG, West JA, Campbell MC. Growth and optical development of the ocular lens of the squid (Sepioteuthis lessoniana). Vision Res 1994;34(17):2177–87. [75] Arnold JM. Closure of the squid cornea: a muscular basis for embryonic tissue movement. J Exp Zool 1984;232(2):187–95. [76] Tomarev SI, Chung S, Piatigorsky J. Glutathione S-transferase and S-crystallins of cephalopods: evolution from active enzyme to lensrefractive proteins. J Mol Evol 1995;41(6):1048–56. [77] Montgomery MK, McFall-Ngai MJ. The muscle-derived lens of a squid bioluminescent organ is biochemically convergent with the ocular lens. Evidence for recruitment of aldehyde dehydrogenase as a predominant structural protein. J Biol Chem 1992;267(29):20999–1003. [78] Komori N, Usukura J, Matsumoto H. Drosocrystallin, a major 52 kDa glycoprotein of the Drosophila melanogaster corneal lens. Purification, biochemical characterization, and subcellular localization. J Cell Sci 1992;102(Pt 2):191–201. [79] Dahm R, Schonthaler HB, Soehn AS, van Marle J, Vrensen GF. Development and adult morphology of the eye lens in the zebrafish. Exp Eye Res 2007;85(1):74–89. [80] Soules KA, Link BA. Morphogenesis of the anterior segment in the zebrafish eye. BMC Dev Biol 2005;5:12. [81] Wistow G, Wyatt K, David L, Gao C, Bateman O, Bernstein S, et al. gammaN-crystallin and the evolution of the betagamma-crystallin superfamily in vertebrates. FEBS J 2005;272(9):2276–91. [82] Xu YS, Kantorow M, Davis J, Piatigorsky J. Evidence for gelsolin as a corneal crystallin in zebrafish. J Biol Chem 2000;275(32):24645–52. K. Jonasova, Z. Kozmik / Seminars in Cell & Developmental Biology 19 (2008) 71–81 [83] Jia S, Omelchenko M, Garland D, Vasiliou V, Kanungo J, Spencer M, et al. Duplicated gelsolin family genes in zebrafish: a novel scinderin-like gene (scinla) encodes the major corneal crystalline. FASEB J 2007. [84] Remtulla S, Hallett PE. A schematic eye for the mouse, and comparisons with the rat. Vision Res 1985;25(1):21–31. [85] Haustein J. On the ultrastructure of the developing and adult mouse corneal stroma. Anat Embryol (Berl) 1983;168(2):291–305. [86] Ihanamaki T, Pelliniemi LJ, Vuorio E. Collagens and collagen-related matrix components in the human and mouse eye. Prog Retin Eye Res 2004;23(4):403–34. [87] de la Cera EG, Rodriguez G, Llorente L, Schaeffel F, Marcos S. Optical aberrations in the mouse eye. Vision Res 2006;46(16):2546–53. [88] Gould DB, Smith RS, John SW. Anterior segment development relevant to glaucoma. Int J Dev Biol 2004;48(8/9):1015–29. [89] Brady JP, Garland D, Duglas-Tabor Y, Robison Jr WG, Groome A, Wawrousek EF. Targeted disruption of the mouse alpha A-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein alpha B-crystallin. Proc Natl Acad Sci USA 1997;94(3):884–9. [90] Brady JP, Garland DL, Green DE, Tamm ER, Giblin FJ, Wawrousek EF. AlphaB-crystallin in lens development and muscle integrity: a gene knockout approach. Invest Ophthalmol Vis Sci 2001;42(12):2924–34. [91] Morrison LE, Whittaker RJ, Klepper RE, Wawrousek EF, Glembotski CC. Roles for alphaB-crystallin and HSPB2 in protecting the myocardium from ischemia-reperfusion-induced damage in a KO mouse model. Am J Physiol Heart Circ Physiol 2004;286(3):H847–55. [92] Ueda Y, Duncan MK, David LL. Lens proteomics: the accumulation of crystallin modifications in the mouse lens with age. Invest Ophthalmol Vis Sci 2002;43(1):205–15. [93] Cuthbertson RA, Tomarev SI, Piatigorsky J. Taxon-specific recruitment of enzymes as major soluble proteins in the corneal epithelium of three mammals, chicken, and squid. Proc Natl Acad Sci USA 1992;89(9):4004–8. [94] Kays WT, Piatigorsky J. Aldehyde dehydrogenase class 3 expression: identification of a cornea-preferred gene promoter in transgenic mice. Proc Natl Acad Sci USA 1997;94(25):13594–9. 81 [95] Nees DW, Wawrousek EF, Robison Jr WG, Piatigorsky J. Structurally normal corneas in aldehyde dehydrogenase 3a1-deficient mice. Mol Cell Biol 2002;22(3):849–55. [96] Hill RE, Favor J, Hogan BL, Ton CC, Saunders GF, Hanson IM, et al. Mouse small eye results from mutations in a paired-like homeoboxcontaining gene. Nature 1991;354(6354):522–5. [97] Quiring R, Walldorf U, Kloter U, Gehring WJ. Homology of the eyeless gene of Drosophila to the small eye gene in mice and Aniridia in humans. Science 1994;265(5173):785–9. [98] Fernald RD. Casting a genetic light on the evolution of eyes. Science 2006;313(5795):1914–8. [99] Nilsson DE, Pelger S. A pessimistic estimate of the time required for an eye to evolve. Proc Biol Sci 1994;256(1345):53–8. [100] Jagger WS. Image formation by the crystalline lens and eye of the rainbow trout. Vision Res 1996;36(17):2641–55. [101] Weber C. Structure histochemistry ontogenetic development, and regeneration of ocellus of Cladonema radiatum Dujardin (Cnidaria, Hydrozoa, Anthomedusae). J Morphol 1981;167:313–31. [102] Nemanic P. Fine structure of the compound eye of Porcellio scaber in light and dark adaption. Tissue Cell 1975;7(3):453–68. [103] Williams DS, McIntyre P. The principal eye of a jumping spider have a telephoto component. Nature 1980;288:578–80. [104] Muller CH, Meyer-Rochow VB. Fine structural description of the lateral ocellus of Craterostigmus tasmanianus Pocock, 1902 (Chilopoda: Craterostigmomorpha) and phylogenetic considerations. J Morphol 2006;267(7):850–65. [105] Yoon CS, Hirosawa K, Suzuki E. Corneal lens secretion in newly emerged Drosophila melanogaster examined by electron microscope autoradiography. J Electron Microsc (Tokyo) 1997;46(3):243–6. [106] Katz MJ. Comparative anatomy of the tunicate tadpole, Ciona intestinalis. Biol Bull 1983;164:1–27. [107] Eakin RM, West JA, Dennis MJ. Fine structure of the eye of a nudibranch mollusc, Hermissenda crassicornis. J Cell Sci 1967;2:349–58.