Download Mesoderm induction in amphibians and chick

J. Biosci., Vol. 21, Number 3, May 1996, pp 353-368. © Printed in India.
Mesoderm induction in amphibians and chick
SURENDRA GHASKADBI*
Division of Animal Sciences, Agharkar Research Institute, Agarkar Road, Pune 411004, India
MS received 3 July 1995
Abstract. Induction is a process in which the developmental pathway of one cell is controlled by
signals emitted from another. Mesoderm induction is the first inductive interaction in the
Xenopus enbryo and probably occurs in all vertebrates. It is a very important event as it is
implicated in the regulation of morphogenesis. Nieuwkoop first demonstrated the importance of
vegetal endoderm in inducing the mesoderm. Slack and co-workers incorporated the information
obtained from experimental embryology in a "three signal" model for mesoderm induction in
amphibians (signals arising from ventral vegetal hemisphere, dorsal vegetal hemisphere and the
organizer). More recent research has resulted in the detection of mesoderm inducing factors
which are members of FGF and TGF--β families. Activin, a member of the TGF-ß family, has
been shown to induce differential gene expression and cell differentiation in a concentrationdependent manner giving credence to the theory of morphogen gradients. Study of mesoderm
induction in the chick embryo is much more difficult due to several reasons. Novel experimental
approaches, however, have been used which point to the role of activin and FGF in chick
mesoderm induction. The demonstration of mesoderm inducing activity of activin and FGF in
other groups of vertebrates, particularly the chick embryo brings out the possibility of a universal
mechanism of mesoderm induction being operative in all the vertebrates.
Keywords. Embryonic induction; mesoderm induction; amphibian embryo; chick embryo;
mesoderm inducing factors; activin; fibroblast growth factor; human seminal plasma inhibin.
1.
Introduction
The fertilized egg undergoes several cleavage divisions resulting in the formation of
a large number of cells. These embryonic cells interact continuously or sporadically
with one another and with the extracellular matrix during morphogenesis (the development of form and shape). Such early cellular interactions include cell adhesion, cell
motility and embryonic induction. It is through early embryonic cell interactions and
sequential inductions that initial, progressive amplification of diversity of cell types is
achieved (Gurdon 1992).
Embryonic induction is a phenomenon wherein one embryonic cell influences the
developmental pathway of another cell in the developing embryo. Ectoderm, mesoderm and endoderm are the three germ layers and it is through inductive interactions
between the prospective ectoderm and endoderm that mesoderm is formed. Mesoderm
induction is one of the earliest inductive interactions. It probably occurs in all
vertebrates (Smith 1988) and is a very important event in animal development
(Asashima 1994). It is also implicated in the regulation of morphogenesis (Gurdon
1987) and appears to be important in neural induction and organization of the body
axis (see Gilbert 1994).
*Fax, 091-212-351542; Email, [email protected].
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Surendra Ghaskadbi
In recent years, mesoderm induction has received considerable attention primarily
because several known growth factors seem to participate in this process. This is at
present an extremely active area of research; consequently, a number of excellent review
articles on this subject have appeared in the last couple of years (for example, see
Asashima 1994; Fukui and Asashima 1994; Kessler and Melton 1994; Klein and
Melton 1994). These reviews, however, concentrate on mesoderm induction in amphibians, particularly Xenopus laevis which is the most widely used model for such studies,
In the last 3-4 years, some studies on mesoderm induction have also been reported for
other vertebrate systems, particularly the chick embryo. Given the conserved nature of
several developmental phenomena throughout the animal kingdom, one would expect
similar, if not identical, basic mechanisms of mesoderm induction to operate in all the
vertebrates. In this article I intend to briefly review mesoderm induction in amphibians,
and using it as background, review corresponding work in the chick embryo. A few
studies on other vertebrates such as mammals and a fish are also mentioned although
they do not allow any definite conclusions. Detailed information on the regulatory
genes in mesoderm induction, which primarily include transcription factor-encoding
genes, is not given here. This can be found elsewhere (Gurdon 1987, 1992; Smith et al
1991; Dawid et al 1992; Knöckel et al 1992; Izpisua-Belmonte et al 1993; Tadano et al
1993; Dawid 1994; Yamada 1994; O'Reilly et al 1995).
2. Mesoderm induction in amphibians
Major work in the area of mesoderm induction has been carried out in the South
African clawed toad Xenopus laevis. The amphibian embryo offers several advantages
as a model system for experimental analyses of developmental phenomena (see, Smith
1989). Earlier work in experimental embryology led to the finding that interaction
between the animal and vegetal pole cells is essential for mesoderm induction. It was
shown that mesoderm originates from the marginal zone (= equatorial cells) under the
influence of the prospective endoderm (Nieuwkoop 1969; Sudarwati and Nieuwkoop
1971; see Gilbert 1994). Thus, isolated animal pole cells will form atypical epidermis in
culture while if co-cultured with cells from the vegetal hemisphere, they will form
mesoderm. Subsequently, Boterenbrood and Nieuwkoop (1973) showed that different
inducing cells from the vegetal half induce different types of mesoderm in animalvegetal combinations. This meant that specific signals are emitted by the vegetal cells
which influence the developmental pathway of prospective ectodermal cells.
2.1
Three signal model
Slack and co-workers proposed a model (figure 1) to explain how mesoderm induction
takes place in the Xenopus embryo (Smith and Slack 1983; Slack et al 1984; Smith et al
1985; Dale and Slack 1987). According to this "three signal" model, the first two signals
for the induction of mesoderm originate in the vegetal hemisphere. One signal
originates from the dorsal vegetal blastomeres (figure 1:DV) and induces dorsal
mesoderm or the organizer which eventually gives rise to notochord and some muscle.
The other signal has its origin in the ventral vegetal cells (figure 1:VV) and it induces
ventral mesoderm which later gives rise to blood, mesenchyme and mesothelium. The
third signal subsequently originates from the dorsal mesoderm (figure 1:O) and
Mesoderm induction
355
Figure 1. The three-signal model. Two mesoderm induction signals are assumed to derive
from the vegetal region of the early blastula. The dorsal-vegetal (DV) signal induces dorsal
mesoderm, or 'organizer' tissue (O) while the ventral vegetal signal (VV) induces general
ventral mesoderm (VM). The ventral mesoderm then receives a signal from the organizer,
probably during gastrulation, which results in the formation of additional muscle (M3) and
perhaps pronephros (M2); only the most remote tissue (Ml) remains as ventral blood-forming
mesoderm. (Reproduced from Smith 1989 with permission of the author and Company of
Biologists Limited).
traverses laterally in the prospective mesoderm germ layer. It exhibits a dorsalizing
effect with the result that the ventral mesoderm is made to form muscle, pronephros
and blood (figure 1:M1-M3).
2.2 Mesoderm inducing factors (MIFs)
It is not sufficient to know that three (or more?) distinct signals may participate in
mesoderm induction. It is essential to identify the nature of the individual signals.
Research over the past 8 to 10 years has mainly been concentrated on this aspect and
has been quite rewarding.
One of the most popular methods to assess the mesoderm inducing activity of
a chemical/growth factor is the animal cap assay (see figure 2). This assay makes use of
the fact that Xenopus animal cap cells, when cultured in isolation, form atypical
pidermis. However, if allowed to grow in a medium containing MIF(s), mesoderm is
induced in these cells, which can be assessed by employing histological and/or
molecular techniques. For methodological and technical details about purification and
assay of MIFs from vertebrate embryos, readers are referred to a review by Smith
(1993).
The animal cap assay may be able to tell us if a particular chemical is capable of
inducing mesoderm. This does not necessarily mean that it actually is an endogenous
ΜIF. An endogenous MIF should fulfill the following criteria (Klein and Melton 1994).
(i) Presence of the factor at the proper time and proper location.
(ii) Presence of receptors for the factor in the responsive tissue.
(iii) Restriction of activity of the factor and/or the receptor in some way so that only
a subset of cells is diverted to a particular fate. In other words, some control mechanism
to stop the whole animal pole from becoming 'mesodermalized'.
(iv) Demonstration of developmental abnormality as a consequence of blockage of the
endogenous signaling pathway.
Some growth factors have been found to fulfill the criteria listed above to a greater or
lesser extent. These are either isomers of the fibroblast growth factor (FGF: Kimelman
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and Kirschner 1987; Slack et al 1987) or members of the transforming growth factor
β (TGF-β: Ruiz i Altaba and Melton 1989; Asashima et al 1990; Smith et al 1990; Köstcr
et al 1991; Jones et al 1992) family. The products of wnt and noggin also participate in the
formation and patterning of mesoderm, though they do not induce mesoderm per se
(McMohan and Moon 1989; Smith and Harland 1991; Kimelman et al 1992; Christian and
Moon 1993; Smith et al 1993). The likely candidates for endogenous MIFs and agents
which can affect the mesoderm pattern are listed in table 1.
Figure 2. Diagrammatic representation of the animal cap assay and explants after activin
treatment. Depending on the activin concentration, many mesodermal tissues from ventral
type mesoderm (low concentration of activin treatment) to dorsal type of mesoderm (middle or
high concentration of activin treatment) are induced (Asashima et al 1990; Ariizumi et al
1991a, b; Nakamura et al 1992; Fukui et al 1993). High concentration of activin also induced
the beating heart in the explant (Moriya and Asashima 1992) and the combination of activin
and retinoic acid induced the renal tubules (Moriya et al 1993). (Reproduced from Fukui and
Asashima 1994 with permission of the author and UBC Press).
Table 1. Factors important in the induction and pattern formation of
mesoderm.
Mesoderm induction
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Figure 3. Diagram of regulation of mesoderm-inducing factor (MIF) and signal transduction.
Activins bind with follistatin to make inactive form. MIFs activate their own receptors to
transfer their signals into the cytoplasm and nucleus to express the early response genes and
retinoic acid (RA) modulates the MIFs signals. (Reproduced from Fukui and Asashima 1994
with permission of the author and UBC Press).
Slack (1993) has critically discussed the roles of these factors during mesoderm induction
and has come out with the plausible explanation that the DV signal (see figure 1) is activin
with possible contribution from wnt and noggin while VV signal is FGF or bone
morphogenetic protein (BMP). The possible mechanism of mesoderm induction by activin
and F GF is depicted in figure 3 (Fukui and Asashima 1994).
Of the factors found to be important in mesoderm induction (table 1), activin is particularly interesting because it can induce different types of mesoderm at different concentra
tions (Green and Smith 1990; Ariizumi et al 1991a, b; Green et al 1992: see figure 2). This
ability of activin supports the morphogen gradient theory proposed by Wolpert, way back
in 1969 (Wolpert 1969). Recently, elegant experiments carried out in Gurdon's laboratory
(Gurdon et al 1994) have demonstrated that activin can exert its differential concentrationdependent mesoderm inducing effect also in intact embryonic tissues. This makes activin
one of the strongest candidates for the role of an endogenous MIF.
The above discussion on mesoderm induction in amphibians only highlights the major
aspects of the problem and is in no way complete. Details about the various experimental
approaches, their rationale and interpretations of the data may be found in some of the
review articles on the subject (for example, see Smith 1989; Slack 1993; Asashima 1994;
Fukui and Asashima 1994; Kessler and Melton 1994; Klein and Melton 1994).
3. Mesoderm induction in chick embryo
Chick embryo is yet another favourite model of developmental biologists. One of the
major reasons for this is that the early chick embryo can be easily explanted and
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successfully cultured in vitro for several hours (for example, by using the single ring
technique of New 1955). The early morphogenesis can thus be monitored in the
laboratory and developmental effects of growth factors and other chemical and
physical agents can be assessed. Furthermore, various types of grafting experiments can
be done using such cultures.
The chick embryo differs from an amphibian embryo in several respects. Unlik the
round frog embryo, the chick embryo is a flat disc of cells that receives its nutrients from
yolk reserves which are predominantly extracellular. The sequence of morphological
changes in the normal development of a chick embryo have been described by
Eyal-Giladi and Kochav (1976: from cleavage to primitive streak formation) and by
Hamburger and Hamilton (1951: freshly laid egg at prestreak stage till hatching). Due
to the basic differences in the shape and topography of the embryo, it is difficult to
explain mesoderm induction in the chick embryo with the three signal model proposed
for the amphibian embryo (figure 1).
The early chick blastoderm is round and flat in shape, It consists of two distinct
areas, the inner area pellucida and the outer area opaca. The two are separated by
a narrow marginal zone. It is important to note here that the marginal zone οf an
amphibian embryo and that of a chick embryo are non-homologous (see Eyal-Giladi
1992). A group of cells attached to the posterior end of the marginal zone is known as
the Koller's sickle. The central area pellucida consists of two germ layers, the upper
epiblast and the lower hypoblast. Cells from the marginal zone and the inductive
hypoblast interact with the competent epiblast to form the primitive streak (Waddington 1932; Azar and Eyal-Giladi 1981) which is the source of mesoderm and endoderm
in the avian embryo (Khaner 1993).
3.1 Problems in assessing mesoderm induction in the chick embryo
In the chick embryo, it is difficult to distinguish between the induction of the primitive
streak and the induction of mesoderm since the former is the source of the latter (Stern
1992; Khaner 1993). The situation is further complicated due to the early mixing of
different cell types during development which makes the assessment of mesodoerm
induction very difficult. Clear cut assays for mesoderm induction, like those available
for the amphibian embryo, are difficult in this system also because of the lack of cell
type specific markers (Slack 1991). In spite of these difficulties, however, novel
experimental approaches have allowed the identification of possible MIFs in the chick
embryo.
3.2 Role of activin
Mitrani and co-workers have carried out a number of studies to detect factors
important in mesoderm induction in the chick. Mitrani and Shimoni (1990) showed
that conditioned medium derived from the Xenopus XTC cell line that induces
mesoderm in isolated Xenopus animal caps (Smith 1987) is capable of inducing
formation of axial structures (notochord and rows of bilaterally symmetric somites) in
isolated chick epiblasts. In the same experiment, basic FGF, epidermal growth factor,
TGF-β1, TGF-β2 and retinoic acid failed to bring about a similar effect. The XTC
derived growth factor called as XTC-MIF was found by Smith et al (1990) to be
Mesoderm induction
359
a homologue of mammalian activin A. Isolated chick epiblasts cultured in the absence
of activin can form only non-axial mesoderm (e.g., blood islands).
AT G F-β like mesoderminducing factor from mouse macrophage cell supernatents,
which is similar to activin (Thomsen et al 1990) and can induce head structures in
Xenopus (Sokol et al 1990), has been shown to induce notochord, somites and neural
tube in isolated epiblasts from chick blastulae (Mitrani et al 1990b). Mitrani et al
(1990b) cloned a fragment of activin ßA chain gene from chick genomic DNA using
degenerate PCR primers and showed that the transcription of activin coincides with
the induction of axial mesoderm. The results demonstrated the body axis inducing
capacity of activin as well as its (activin Β) active transcription at the proper time and at
the proper location within the embryo.
In a subsequent study from the same laboratory (Ziv et al 1992) it was shown that
activin containing medium can generate ectopic axial structures in chick blastoderm
explants. These results mean that activin is not a permissive inductor but an instructive
one (see Slack 1993). It was further suggested that regulatory processes operate in
normal development which ensure the formation of a single axis. More recently,
presence of TGF -ß2 and TGF -ß3 as well as Vgcl (chick homologue of Vg-related gene
vgrl) in the early chick embryo has been reported (Harris et al 1993).
Recent studies from our laboratory in the chick embryo show that activin-related
molecules continue to participate in the later development of the mesoderm, for example in
somitogenesis (V Patwardhan and S Ghaskadbi, unpublished results). This is consistent
with the recent finding that importance of activin-related signaling pathway is not
onfined to pregastrulation stages of the chick but may continue to be important in later
developmental stages of mesoderm, limbs and nervous system (Stern et al 1995).
3.3
Role of FGF
In order to assess the role of FGF in mesoderm induction in the chick embryo,
inhibitors of FGF action have been employed. Mitrani et al (1990a) showed that
heparin and suramin, inhibitors of FGF, block the formation of mesodermal structures
in chick embryo in a dose- dependent manner. These authors further demonstrated the
presence of basic FGF RNA and protein at pregastrula stages. While FGF is incapable
of inducing axial mesoderm in the chick embryo, it may well induce the non-axial
mesoderm (Mitrani et al 1990a). Since non-axial mesodermal tissue (blood) can form in
isolated epiblast cells (Mitrani and Shimoni 1990), one can appreciate why isolated
chick epiblasts can not be used to assess the mesoderm inducing ability of such
potential inducers.
Gordon-Thomson and co-workers (Gordon-Thomson et al 1991;Gordon-Thomson
and Fabian 1994) have shown that basic FGF plays an important role in the induction
of non-axial mesoderm (blood). Their studies show that the inhibitory effect of heparin
on erythropoiesis can be alleviated by the action of FGF (Gordon-Thomson et al
1991). It has been suggested that the induction of haemoglobin (used as a marker for
blood tissue) in the epiblast by the hypoblast is mediated by basic FGF (GordonThomson and Fabian 1994).
Due to the technical difficulties in assessing mesoderm induction in the chick
embryo, Cooke and Wong (1991) devised indirect methods which made use of cultured
chick epiblast cells and whole early chick blastoderms. While activin-like factors, basic
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FGF and TGF-ß 2 exhibited strong mesoderm inducing activity, platelet derived
growth factor (PDGF) was inactive in this respect.
3.4 Mesoderm enhancing effect of human seminal plasma inhibin
It has been generally accepted that certain regulators of mesoderm induction need to be
present in the developing embryo. Such regulators would be necessary to control the
process of mesoderm induction and save the whole embryo from becoming 'mesodermalized'. While activins bring about the release of follicle stimulating hormone and
erythroid differentiation in the adult organism, inhibins exhibit an exactly opposite
effect; they inhibit both, the release of follicle stimulating hormone as well as erythroid
differentiation. A possibility was therefore suggested that inhibins could act as endogenous inhibitors of mesoderm induction (Smith et al 1990). However, inhibin
A (Mol. wt. 32 kDa) was shown to have little (Asashima et al 1990) or no effect
(Thomsen et al 1990) on mesoderm induction in Xenopus.
We have assessed the possible inhibitory effects of another inhibin, the human
seminal plasma inhibin (HSPI), on the formation of mesoderm in the chick embryo
(Ghaskadbi et al 1994). HSPI (figure 4), purified from human seminal plasma is
a 10 5 kDa peptide made up of 94 amino acids (Thakur et al 1981; Seidah et al 1984;
Sheth et al 1984; Ackland et al 1992). In our studies, whole, gastrulating chick embryos
cultured in vitro were treated with HSPI and their development was monitored over
a period of about 20 h for any deviation from the normal pattern. It is important to note
here that the specification of axial/dorsal mesoderm in the chick embryo continues
even up to the beginning of neurulation (Stern 1992). Contrary to expectations, HSPI
was found to enhance the development of somites and heart, structures of mesodermal
origin, in some of the treated embryos (figure 5; also see Ghaskadbi et al 1994). In other
embryos the stimulation of development was sometimes associated with abnormalities
in the anterior region of the embryo while in some embryos, treatment with HSPI
resulted in completely abnormal development (figure 6; also see Ghaskadbi et al 1994).
Figure 4. The amino acid sequence of human seminal plasma inhibin (HSPI). The synthetic
nonapeptide fragment (C-NP) consists of amino acids 86-94. (Reproduced from Ghaskadbi
et al 1994 with permission of Publications and Information Directorate, Council of Scientific
and Industrial Research, New Delhi).
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Histological examination of control and HSPI-treated embryos not only confirmed
the above-mentioned gross morphological observations but also brought out some
interesting facts (figure 6). In HSPI-stimulated embryos (figure 6H), the compaction of
somites was much more prominent indicating advanced differentiation as compared to
the somites of the control embryo (figure 6G). The diameter of the neural tube was also
considerably reduced in HSPI-treated embryos and consequently the notochord was
displaced (figure 6H). Comparison of transverse sections passing through the anterior
region of the embryos (figure 6D-F) revealed presence of some loose cells on the
Figure 5. For caption, see p. 362.
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Surendra Ghaskadbi
Figure 5. Mesoderm enhancing effect of HSPI and C-NP in chick embryo explants cultured
in vitro. (A) Diagrammatic representation of a chick embryo to show how anteroposterior
length measurements were made. HT, heart; HF, head fold; Β A, body axis. (B-Ε) Stimulation of
development of somites (B), length of body axis (C), length of head fold (D) and length of heart
(E). a-e represent embryos treated with saline (control: a), 10 ng/embryo HSPI (b), 1 ng/embryo
HS PI (c), 10 ng/embryo C-NP (d) and 1 ng/embryo C-NP (e). The vertical bars represent 95%
confidence limits. (Part A reproduced from Ghaskadbi et al 1994 with permission of Publications and Information Directorate, Council of Scientific and Industrial Research, New Delhi;
Parts B-Ε based on Ghaskadbi et al 1994).
dorsolateral sides of the neural tube in HSPI-stimulated embryos (figure 6E). These
could be migrating neural crest cells, once again indicating advanced development;
specific markers, however, need to be used to confirm this observation. Antiserum to
Mesoderm induction
Figure 6. For caption, see p. 364.
363
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Surendra Ghaskadbi
HSPI strongly inhibited the normal development of the chick embryos (Ghaskadbi
et al 1994) These results strongly indicate that HSPI-related molecules may participate
in the regulation of mesoderm formation in the chick embryo. Experiments are in
progress to study if HSPI can indeed induce/modulate the expression of mesodermspecific marker genes in the chick embryo.
Interestingly, a synthetic C-terminal nonapeptide fragment of HSPI (C-NP)
mimicked the mesoderm enhancing effect of HSPI (figure 5). Based on the potent
mesoderm enhancing effect of C-NP, it is tempting to suggest that a small fragment of
the parent molecule may be responsible/sufficient for the lalter's mesoderm enhancing
effect. If this conjecture can be vindicated experimentally, we might get closer to explain
the mesoderm inducing activity of a large number of related molecules such as
XTC-MIF, activins, TGF-β 2, TGF-β3, bone morphogenetic proteins, etc.
4. Mesoderm induction in other vertebrates
Little information is available about the formation of mesoderm in mammalian
embryos. TGF-β and bFGF have been shown to initiate embryonic gene expression
and promote the development of bovine embryos in vitro (Larson et al 1992). In mouse
embryos and embryonic stem cells, activin is expressed at a time when mesoderm.
induction begins (Albano et al 1993) raising the possibility of their function in mesoderm induction. Presence of activin in the murine blastocysts has been confirmed
recently (Paulusma et al 1994). More recently, the expression of mRNAs for activin
receptors in oocytes, pregastrulae and gastrulae of mouse has been reported (Manova
et al 1995). Basic FGF has been shown to be able to induce the formation of the
primitive streak in rabbit blastocysts in vitro indicating a role for FGF in mammalian
mesoderm formation (Hrabe de Angelis and Kirchner 1993). One of the wnt genes wnt genes
wnt-3a, appears to be essential for mesoderm formation in the mouse embryo (Takada
et al 1994). These studies indicate that similar MIFs and mesoderm modifiers/regulators may participate in mammalian mesoderm induction. Extensive studies will
however, be required to prove this point unequivocally.
Activin of maternal origin has been shown to be necessary for mesoderm and axis
formation in a fresh water fish, the Japanese medaka (Wittbrodt and Rosa 1994). The
authors propose that mechanisms for mesoderm and axis formation and MIFs are
conserved in lower vertebrates. To my knowledge, no information is available on
mesoderm formation in a reptilian embryo.
Figure 6. Histological examination of HSPI-treated embryos. (A) Control embryo. (B)
HSPI-treated embryo showing stimulation of development of mesodermal structures without
any apparent abnormality. (C) \HSPI-treated abnormal embryo. (D) Τ S through anterior
region of a control embryo like in (A). Note normal histological features. (Ε) Τ S through
comparable region of an embryo like in (B), Note normal histological features except the
mixing of neural and non-neural ectodermal cells. (F) Τ S through comparable region of an
embryo like in (C). Note open neural tube and general disruption of cellular organization.
Analysis of Τ S through comparable regions of the three types of embryos reveals more
compact somites and a neural tube with smaller diameter in stimulated embryo (H) as opposed
to the control embryo (G). Τ S through abnormal embryo (I) shows open neural tube and
disorganized mesoderm. Scale bar = 1 mm approx. for A-C, 125 µm for D-F and 50 µm for G-I.
(Reproduced from Ghaskadbi et al 1994 with permission of Publications and Information
Directorate, Council of Scientific and Industrial Research, New Delhi).
Mesoderm induction
365
5. Conclusions
Despite several differences in the morphology and geometry of the embryos of Xenopus
and chick, similar mechanisms of mesoderm induction seem to operate in the two systems.
Assessment of mesoderm inducing activity of various factors is relatively more difficult in
the chick embryo. Novel experimental approaches, however, have been successfully
employed to at least partially overcome these problems. Activin almost certainly is one of
the endogenous MI F in both frog and chick. FGF appears to be another endogenous MIF,
capable of inducing only the ventral mesoderm. As evident in the chick embryo, it is
possible that molecules similar to human seminal plasma inhibin may participate in the
regulation of mesoderm formation. The mesoderm inducing ability of activin and FGF in
in vitro assays, the ability of activin to induce ectopic axial structures and temporal and
spatial expression of activin and FGF in both the systems, Xenopus and chick embryos,
point to the existence of a universal mechanism of mesoderm induction in vertebrates.
Acknowledgements
I am grateful to Drs Hemant Ghate, Jayanta Pal, Vidya Patwardhan and Charu Shinde
for stimulating discussions and comments on the manuscript. Our work was supported
by the Department of Science and Technology, New Delhi.
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