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Development 104 Supplement, 17-27 (1988) Printed in Great Britain @ The Company of Biologists Limited 17 1988 Phenotypic comparison between maternal and zygotic genes controlling the segmental pattern of the Drosophila embryo RUTH LEHMANN* MRC Laboratory of Molecular Biology, Cambridge CB22QH, UK and Max Planck Institut filr Entwicklungsbiologie III, 74 Ttibingen FRG *Present address: Whitehead Institute, Nine Cambridge Center, Cambridge MA 02142, USA Key words: Drosophila embryo, segmental pattern, maternal gene , zygotic gene lntroduction The longitudinal pattern of the Drosophila embryo is controlled by the concerted activity of gene products provided duritrg oogenesis (maternally active genes) and embryogenesis (zygotically active genes). An initially relatively coarse system of positional information laid down by maternal gene products becomes successively refined towards the repeating pattern of segments first by the division into domains by the products of the zygotic gap genes and subsequently by the action of pair-rule and segment-pol arity genes (Ni.isslein-Volhard & Wieschaus, 1980; Ingham & Martinez-Arias, 1986; Ingham, 1988; for review see Akam , 1987). Maternal genes affecting anteroposterior pattern have been classified into three groups according to their phenotype: the terminal group, the anterior group and the posterior group (NiissleinVolhard et al. I9B7). Together the three maternal gene groups control the establishment of the entire segmental pattern. Embryos that lack all maternal information show no anteroposterior pattern (Ntisslein-Volhard et al. 1987, R.L. unpublished data). The information provided by the maternal genes is interpreted by tygotic genes. The best candidates for genes that may directly respond to the maternal signals are the zygotic gap genes (Table 1; NtissleinVolhard & Wieschaus, 1980). The number of genes with a 'gap' phenotype is small and each gap gene has a distinct phenotype. Similar to mutations in the gap mutations cause large continuous deletions including several consecutive segments maternal genes , while the remaining structures are relatively normal. In this article, I would like to summarize and discuss some of the results concerning the establishment of positional information in the egg cell and its interpretation by differential activation of. zygotic genes. The first part deals with the properties of the posterior group genes as they have been characterized genetically as well as by fate-map analysis. This description should provide some idea about the methods used to characterize phenotypic groups. In the second part, these results will be compared to similar studies on the anterior and terminal group. The goal of this article is to point to the relative roles maternal anteroposterior genes and zygotic gap genes play in the generation of the segmented pattern. The maternal posterior group genes and the zygotic gen e knirps are part of the same developmental pathway Mutations in eight diferent genes affect the segmentation of the embryonic abdomen: knirps (NtissleinVolhard & Wieschaus, 1980; Jtirgens et al. 1984), tudor (Boswell & Mahowald, 1985) , vasa, valois, staufen (Schtipbach & Wieschaus, 1986), oskar, pumilio and nanos (Lehmann & Nilsslein-Volhard, 1986 , 1987 a, unpublished data). To test whether the products of all eight genes are involved in the same developmental pathw?y, I studied the lethal phenotype and its origin for each locus. (A) The embryonic lethal phenotype Fig. 1 shows the strongest phenotypes produced by mutations in one of the maternal posterior group genes , nanos, and the zygotic gene knirps (for the wild-type pattern refer to Fig. 1). Embryos derived from nanos females lack all abdominal segments while the regions anterior and posterior to the abdomen, the head-thorax region and the telson, respectively, appear normal. However, in embryos mutant for a strong kni allele, two abdominal segments are formed. The first abdominal segment is 1B R. Lehmann Table 1. Maternal and zygotic genes affecting the anteroposterior pattern Zygotically active Maternally active Map Gene Anterior position* Gene Phenotype bicoid 84A Deletion of head and thorax, acron transformed to telson exuperantia swallow 578 5E Weak anterior deletions oskar 85A vasa 35C tudor 57B_D staufen valois 55A_F 38A_E nanos 92A pumilio 85C hunchback Map positionx 85A Phenotype Deletion of thorax and gnathal region, acron present, pA7 and A8 missing Posterior Terminal torso 43E trunk 31A-C torsolike fs(1) polehole fs(I) Nasrat l(1) polehole 93 5CD knirps 778-F Deletion of most of the abdomen. A8 present Deletion of abdomen (excluding telson) and pole plasm lgiant 3,A. Deletion of abdomen i Denticle band of A5-7 deleted. Also anterior deletion] pole plasm present tailless 100A Deletion of acron and telson, excluding stomodeum and proctodeum Deletion of acron and telson 2AB 2F Krilppel 61F Deletion of thorax and anterior abdomen. Malpighian tubules missing * Cytological mapping. Juxtaposition of maternal and zygotic genes of similar phenotype affecting the antero-posterior pattern. This table shows that several maternal genes share phenotypic similarities with one zygotic gene. The gene giant has been tentatively assigned to the posterior group because mutant embryos have defects in the abdominal region in addition to defects in the thorax and labium (Petschek et aI. 1987). enlarged and more rows of denticles are formed than in a wild-type abdominal segment (14-L6 instead of 6-7 in the wild type). Morphologically this segment resembles a first abdominal segment, but by genetic criteria (double mutant combinations with various mutants of the Bithorax-Complex) it seems that this segment is of mixed segmental identity (A1-A5). The entire field acquires thoracic morphology only in kni embryos which lack Ubx and abdA (Sanch ez-Hetrero et al. 1985) but not in double mutants between kni and (lbxcl (Casanova et al. 1988). The second abdominal segment formed by a knirps embryo corresponds morphologically as well as genetically (complete transformation only in double-mutants with Df(3R) P9 (Lewis , I97B)) to a normal eighth abdominal segment. A11 maternal posterior group genes show the strong phenotype described for nanos. The difference in phenotypic strength between the zygotic and maternal mutants may be due to maternally derive d kni product. To test this idea I compared the phenotype of homozygous kni embryos derived from a germ line homozygous mutant for kni with those derived under normal conditions from a heterozygous germ line. Germ line precursor cells from the progeny of heterozygous kni flies were transplanted into sterile hosts (for method used refer to Lehmann & NtissleinVolhard, 1"987b). The germ lines of four females were homozygous and those of twelve were het erozygous for kni (total number of fertile females - 34). No difference in the mutant phenotype could be detected between the mutant progeny. The kni gene seems thus to be expressed exclusively by the embryo itself. Weak alleles have been identified for kni (Ji.irgens et al. 1954) and all seven maternal loci (Boswell & Mahowald, 1985; Schtipbach & Wieschaus, 1986; Lehmann & Ntisslein-Volhard, 1986, 1987a, unpublished data). It is thus possible to compare the effect residual gene activity of any given locus has on the final mutant pattern. The hypomorphic series of all seven maternal genes is basically identical and has been described earlier for the oskar allele osk3oL . Maternal and zygotic gene control of Drosophila segmentation With increasing phenotypic strength segments are lost from the middle region of the abdomen (,4.4-,4'6) while the first and the eighth abdominal segment are most insensitive to variations in gene activity (Fi g. 2). The phenotype of the strong, intermediate and weak kni alleles are found as intermediates of the maternal series (comp are Fig . 2A-D,B-E,C-F). The strong phenotypic similarities between the maternal genes and kni suggest a common role these genes play for the development of the embryonic abdomen. (B) Effect on development and fate map Since the final lethal phenotype is the consequence of an early developmental misrouting it is necessary to study the origin of the pattern abnormalities observed Fate-map changes in the abdominal region are difficult to detect during early development of mutant embryos because no morphological markers can be used. The anterior and posterior dorsal folds, for example, are formed in strong mutant embryos and the head fold is at its normal position in all mutants with the exception of stau where it forms more anteriorly (Schiipbach & Wieschaus, 1986) . Shortly after the onset of gastrulation mutant embryos deviate from wild type as they do not fully extend the germ band to the dorsal side. in the cuticle pattern. This effect is more pronounced in the strong maternal mutants than in kni embryos. Later during development localized cell death occurs in the abdominal region of all maternal mutants and kni. At the blastoderm stage and thus prior to any morphological deviation from wild-type development , fate map changes can be detected in mutant embryos probed with polyclonal antibodies directed against the product of the segmentation gene fushi tarazu (ftz) (Carroll & Scott, 1985 , 1986; CarroII et al. 1986). In wild-type embryos at this stage , ftz protein is expressed in seven transverse stripes separated by stripes of non-expressing nuclei (Fig. 3A). Each stripe is about 3-4 nuclei wide, while the seventh ftz expressing stripe is 5-6 nuclei wide. The repeating pattern of. ftz expression can be used to map the segmental primordia. The primordium of the abdomen spans from the middle of the third stripe (parasegment 6, Martinez-Arias & Lawrence, 1985) to the anterior border of the last stripe (parasegment 14) corresponding to a region between 50 % and 20 % egg length (0 % egg length corresponds to the posterior pole). For each locus , ftz expression was monitored in embryos of different phenotypic strength (Fig . 4). When we compare the pattern of ftz expression in embryos that would have developed the same late cuticle phenotype, the phenotypic series of all maternal genes is similar. A series of fate map changes leads from the wild-type fate map with about even spacing of sev en 19 ftz expressing stripes in the region % egg length to a dramatically changed fate map in strong mutant embryos (Fig. 38, Carroll et al. 1986). In these only four ftz stripes can betwe en 65 "/" and I0 be detected. The anterior border of the first stripe is at its normal position but the first two ftz stripes and the interstripe are expanded such that each is five to six cells wide instead of three to four in wild type. The third stripe is less intensely stained with the antibody and is only found on the dorsal side. The fourth stripe resembles from its position and size the expression pattern of the last, seventh, wild-type stripe (Fig. 3B). The stripes four to six are missing. The interpretation of the strong mutant pattern is facilitated by the pattern of expression in embryos of intermediate phenotype (Fig.3D,F,H). In the abdominal regioil, the size of the ftz expressing and nonexpressing regions becomes reduced to one to two cells in embryos that would show single segment deletions (Fig. 3H). In stronger mutant embryos, the three stripes are fused into one, or less frequently two, broad regions of expression (Fig. 3D,F) and finally in the strongest phenotype they disappear. In the abdominal region, we thus observe a fusion of metameric primordia into enlarged units while in the thoracic region (first three stripes) segmental primordia seem to expand harmoniously towards the posterior with decreasing in gene activity (Fig. 5). A11 maternal mutants show the same fate map shifts with the exception of mutant staufen embryos (Figs 4 and 5). stau mutations cause an expansion of the thoracic region towards anterior and posterior. In the most extreme mutant phenotype, the region between the first and the third stripe (which correspond to the primordia of the posterior maxilla, the labium and the first, second and anterior third thoracic segments) extends from 75 % to 40 % egg length instead of 65 % to 48 % inwild type (Fig. 5). In the abdominal region, segments are compressed and finally lost in a pattern very similar to that observed in other maternal genes (Fig . 4). Genetic and molecular results suggest that the effect stau mutations have on the anterior fate map reflects the role of stau in the locahzation of bicoid product (Driever & Ntisslein-Volhard , IgBBb; R.L. unpublished data). The allelic series f.or knirps is rather similar to that described for the maternal mutants (Fig . 4) but, interestingly, changes in the fate map are restricted to the abdominal region while the thoracic region is not affected (Fig. 5). In extreme kni mutants, two ftz stripes of normal position are followed by an enlarged third stripe of normal intensity which encompasses the circumference of the embryo and a last stripe most likely resembling the normal seventh stripe (Fig. 3C) (see also Ingham & Gergen, this volume). In weak and intermediate phenotypes, segmental 20 R. Lel'trnann Maternal and zygotic gene control of Drosophila primordia in the abdominal region are compressed and lost in a sequence similar to that described for the maternal genes (compare Fig. 3C-D,E-F,G-H). Our studies on the phenotype, fate map and development of mutant kni embryos and embryos derived from females mutant for each of the maternal posterior group genes indicate a common basis for the late mutant phenotype. In all mutants, we can detect similar fate-map changes in the abdominal region at the blastoderm stage (2'5h after egg deposition). These fate-map changes presumably lead to the generation of enlarged segmental primordia in which cell death occurs later during development. Thus we can visuali ze the final cuticle phenotype as the consequence of a primary defect in the blastoderm fate map and a later-occurring size-regulative process. (C) Maternal-zygotic interactions The wild-type function of all maternal posterior group genes is required for an abdomen-specific activity localized at the posterior pole (Lehmann & Ni.isslein-Volhard, 1986, 1987 a, unpublished data). Transplantation of posterior pole plasm from a wildtype embryo into the abdominal region rescues the Fig. L. The phenotype of maternal mutants and zygotic gap mutants affecting the anteroposterior pattern. (A) Wild type. Cuticular derivatives of the acron and the head segments are the labrum, the cephalopharyngeal skeleton and the sensory organs (maxilla and antenna) all situated either inside or at the very anterior tip of the larva. Segmentation is seen clearly in the three thoracic and eight abdominal segments. The telson at the posterior shows no segmental organtzatton, its most prominent structures are the Filzkorper and spiracles that mark the posterior opening of the trachea, the anal plate and the anal tuft (for detailed description refer to LohsSchardin et al. 1979; Jiirgens et al. 1986; Jtirgens, L987). (B-C) The posterior group: A11 (B, maternal phenotype) or most (C, zygotic phenotype) abdominal segments are deleted. (B) Embryo derived from female mutant for nosLT . (C) Embryo homozygous mutant fot kniIIIE4s . (D,E) The terminal group: Embryos in D (maternal phenotype) and E (tygotic phenotype) lack the most anterior and posterior structures, the head skeleton is smaller and FilzkorPef, anal plate and spiracles are missing. (D) Embryo derived from female homozygous for torwK. (E) tlPlq embryo. (F,G) The anterior group: thorax and head structures are missing. (F) Maternal phenotype. Embryo derived from homozygous mutant bcdEt female, the acron is replaced by a second telson. (G) Zygottc phenotype. Homozygous 7r6tar embryo derived from a homozygous hb germ line. The posterior abdomen is duplicated anteriorly, the arrow heads point anteroposteriorly. The star demarcates a second phenotypic trait characteristic fot hb, the naked cuticle of A7 and the denticle band of A8 are deleted. (H) Embryo homozygous mutant for Ky'. cp, cephalopharyngeal skeleto fl, t, thorax ; a, abdomen , t€ , telson ; fk, Filzkdrper. segmentation 2l abdominal phenotype of the maternal posterior group mutants. For osk mutants, a quantitative relationship between the activity found at the posterior pole and the degree to which abdominal segmentation is affected can be established. Strong mutant embryos contain no activity while weak alleles have residual activity (Lehmann & Ntisslein-Volhard, 1986). The transplantation experiments further indicate that the distribution of the signal from its source, the posterior pole to its target at the abdominal region is graded from posterior to anterior (Lehmann & Ni.isslein-Volhard , 1987 a). The harmonious expan- sion of the thoracic primordia in parallel to the enhancement of the mutant phenotype further suggests that the requirements for the signal are different along the anteroposterior axis. The fusion of segmental primordia in the abdominal region, on the other hand, does not follow a strict anterior-posterior pattern (see above) and may suggest different requirements of the posterior signal for the activation andf or repression of kni and neighbouring gap genes, such as Kr and giant (Petschek et al. 1987), which affects the development of the sixth through seventh abdominal segment (see legend of Table L). The differences between the phenotype of kni and the maternal genes indicate that the maternal genes do not exclusively act on the expression of. kni. The effect of the maternal mutants on thorax development may well reflect the role that the maternal genes play in controlling the expression pattern of Krtippel. affects the development of the thorax and the anterior abdomen (Fig. LH; Wieschaus et al. 1984) and the Kr protein is expressed at early blastoderm in a region between 39 % and 55 % egg length (Gaul et al. 1987). The Kr protein domain is expanded quite prominently towards posterior in embryos lacking the maternal posterior gene products and only slightly enlarged in kni (Gaul & Jlickle, 1987). Kr hunchback and tailless share phenotypic similarities with the anterior and terminal group of maternal genes Studies on the anterior and terminal group of genes suggest that direct relationships similar to those between the posterior group genes can be established between maternal and zygottc gap genes on the basis of phenotypic analysis and fate mapping. (A) The terminal group Five maternal genes, one gene expressed maternally well as zygotrcally and one zygotically active gene belong to the terminal group: torso (tor), trunk (trk) (Schtipbach & Wieschaus, 1986) ; torsolike (tsl) (Ntisslein-Volhard et al. 1987; Frohnhofer,I9ST), fs(1)I'{asas R. Lehmann 24 e0 rttl 70 50 30 10 o/ /o I Egg length + w m nanos nanos S + w m pumilio bos (') .!m S U) 'aw o+ (-) + w m oskar c) S \{ /, ,rj staufen o< + w m vasa S 111 + w m valois S 100 m tudor S + w m staufen S + h m knirps s Fig. 4. Comparative fate maps of the hypomorphic series of all posterior group genes. The ftz protein expression patterns in mutant embryos of different allelic strength are compared. For each genotype, the strongest (s) phenotype is compared to wild type (+), a medium (-) and a weak (w) phenotype. For kni the weak (*), strong (s) and heterozygous (h) phenotype was recorded. For each phenotype between three and five embryos were drawn with a camera lucida and the position of ftz expressing cells was recorded. The anterior border of the first, the third and the seventh stripe are connected to show the extent of shifts in the fate map. Hatched areas indicate weak stripes, open bars indicate weak expression on dorsal side. The anterior border of the first stripe marks the position of the maxilla and the head fold in wild type, the position of the third stripe overlaps with the posterior part of the third thoracic and the anterior part of the first abdominal segment. The anterior border of the seventh stripe corresponds to the posterior part of A8. Maternal genotypes; nos: nosLT f D\(3R)X43 (s), nosRw f nosRW (m + w); pum: pumuto I pr*aso 1g'C (s), 29"C (m + w); osk: osk166 I OlSn)pxt-Io3 (s), oslCql f oslCql (m + w); vas: vasPD I n(zr)A72 (s), vasota f vasPD (m + w); val: valPE I offzlTW2 (s), valRB f o1z)rw2 (m + w); tud: tudwcs f tudwcs; stau: stauD3 f Df(2R) PC4 (s), sra r"t I ttauD3 (m + w); zygotic genotypes: kni: 1rn{IID f kniIIID (s), knilaF f kn/aF (-), kniF'f + . l'rl 90 80 70 60 50 40 30 20 10 0 Egg length (%) + w knirp's Fig. 5. Graphic interpretation of fate map changes in nanos , staufen and knirps. The position of the anterior border of each ftz strtpe is marked and corresponding stripes are connected within each hypomorphic series (+, wildtypei w, weak; m, intermediate; s, strong). The identity of each stripe was deduced from its position and from the pattern of deletions observed within the series. The change in position of a given stripe along the longitudinal axis depends on the allelic strength. The shift in position is harmonious within the thoracic region in nos and stau. In stau embryos, the thoracic region gets expanded anteriorly and posteriorly. The fate map of the thoracic region is unaffected in mutant kni embryos. data) support the similarities in phenotype. In hb and bcd mutant embryos, the two anterior stripes of. ftz expression are deleted while the third stripe marking the border between thorax and abdomen is expanded towards anteriorly. The extreme hb phenotype is only produced by homozygous mutant embryos derived from a homo- zygous mutant germ line. Such embryos form a normal acron but almost all head structures and the thorax and anterior abdomen are deleted. The posterior abdomen is duplicated anteriorly with the plane of mirror-image duplication in the fourth segment (Fig. 1G). The lack of function hb phenotype can thus not be as easily described as a subpattern of the more extreme maternal phenotype. Mirror-image duplications within the abdomen occur rarely in bcd embryos (Frohnhofer, 1987). The occurrence of mirror-image duplications in hb may be due to novel zygotic interactions among the gap genes (Gaul & Jiickle , 1987) caused by the lack of hb product, and may thus point to the important role the maternal and zygotic hb product has for controlling the expression Maternal and zygotic gene control of Drosophila bicoid ANTERIOR hunchback Krilppel nanos POSTERIOR knirps torso TERMINAL tailless ftz pattern fate map 100 90 80 70 60 50 40 30 20 10 0 % egg length Fig. 6. Deletion pattern of maternal and zygotic mutants of the anterior, posterior and terminal group. Each bar represents the pattern of deletion characteristic of either a maternal or a zygottc mutant of the anterior, posterior and terminal group. The hatched areas indicate deletions, the dotted areas indicate replacements of structures, e.g. the duplication of the telson found in bcd, or the duplications of posterior abdominal segments in hb and Kr. At the bottom, &tr rdealized pattern of ftz expression is brought into register with the blastoderm fate map (after Lohs-Schardin et al. 1979; Jiirgens et al. 1986; Ji.irgens, L987; Campos-Ortega & Hartenstein, 1985; Hartenstein et al. 1985). AC, acron; HE, head including pre- as well as gnathal segmentsl T, thorax; A, abdomen; TE, telson. of. Kr and kni during normal development. In contrast to the zygottc expression of hb, which is under bcd control, the distribution of the maternal hb product is under the influence of the maternal posterior group genes (Tautz, 1988). segmentation 25 and anterior group, segments are not lost in a strict anterior-posterior order (Frohnhofer 8. NtissleinVolhard, 1987; this article), while an anterior-posterior order has been described for the terminal group, where with increase in phenotypic strength structures are lost towards the respective pole (Strecker et al. 1988). (3) Mutant phenotypes within a group originate by similar principles (fate-map shifts, expanded segmental primordia, cell death) in the maternal and zygotic mutants (Carroll et al. 1986; Carroll & Scott , L986; Mlodzik et al. I9B7; Mahoney & Lengyel, 1987; Degelmann et al. 1986; Frohnh6fer & Ntisslein- Volhard, 1987; this article). (4) The lack of function phenotype of each zygotic gap gene is less extreme than that of the respective maternal genes. Therefore, each maternal gene seems to control the expression pattern of more than one zygotic gene. This may be achieved by direct activation of other zygotic genes or, as shown for Kriippel,by suppression (Gaul & Jtickle, 1987). A number of maternal genes and almost aII zygotic genes have been analysed molecularly (e.g. Stephenson et al. 1987; Frigerio et al. 1986; Berlethet al. 1988; Driever & Ni.isslein-Volhard, 1988a,b; Preiss et al. 1984; Gaul et al. 1987;Tautz et al. 1987;Tautz, 1,988). The role of specific maternal products for the activation of the zygotic counterparts has thus become amenable to direct molecular investigation. The phenotypic analyses summarized here indicate a com- plex pattern of interactions in order to provide the information required for the establishment of an integrated anteroposterior pattern. I am especially thankful to Phil Ingham for his patience and commentaries on the manuscript. I thank H. Krause for the ftz antibody and A. Cron for help with the preparation of the manuscript. References Conclusions Arau, M. (1987). The molecular basis for metameric pattern in the Drosophila embryo . 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