zen transcripts are distributed along the dorsal surface of precellular embryos, including the anterior and posterior poles. In cross section, transcripts encompass 40% of the circumference. By onset of gastrulation [Images], expression is lost from the poles, and is restriced to 10% of the circumference. Transcripts are detected in portions of the dorsal ectoderm that are anterior to the presumptive ectoderm and might correspond to the future optic lobe. Transcripts are detected in a subset of pole cells within the posterior midgut. There are interesting subtle differences between localization of Z1 and Z2 transcripts (Rushlow, 1987).

Effects of Mutation or Deletion

Advanced stage zen mutants show a twisting along the germ band and a failure of head involution. The phenotype can be explained on the basis of a transformation in cell fate of the dorsal most ectoderm toward a more ventral pathway of differentiation (Rushlow, 1987). In zen mutants, the cephalic furrow [Images] arises from a more dorsal region. Furthermore, the anterior and posterior transverse furrows (dorsal folds) are virtually absent. There is a failure of posterior midgut invagination to extend anteriorly along the dorsal surface. The amnioserosa is absent (Rushlow, 1990).

A genetic network conferring canalization to a bistable patterning system in Drosophila

To achieve the 'constancy of the wild-type,' the developing organism must be buffered against stochastic fluctuations and environmental perturbations. This phenotypic buffering has been theorized to arise from a variety of genetic mechanisms and is widely thought to be adaptive and essential for viability. In the Drosophila blastoderm embryo, staining with antibodies against the active, phosphorylated form of the bone morphogenetic protein (BMP) signal transducer Mad, pMad, or visualization of the spatial pattern of BMP-receptor interactions reveals a spatially bistable pattern of BMP signaling centered on the dorsal midline. This signaling event is essential for the specification of dorsal cell fates, including the extraembryonic amnioserosa. BMP signaling is initiated by facilitated extracellular diffusion that localizes BMP ligands dorsally. BMP signaling then activates an intracellular positive feedback circuit that promotes future BMP-receptor interactions. This study identified a genetic network comprising three genes that canalizes this BMP signaling event. The BMP target eiger (egr) acts in the positive feedback circuit to promote signaling, while the BMP binding protein encoded by crossveinless-2 (cv-2) antagonizes signaling. Expression of both genes requires the early activity of the homeobox gene zerknullt (zen). Two Drosophila species lacking early zen expression have high variability in BMP signaling. These data both detail a new mechanism that generates developmental canalization and identify an example of a species with noncanalized axial patterning (Gavin-Smith, 2013).

This study has identified a genetic network that acts as a phenotypic stabilizer of a spatially bistable patterning process. The minimal bistable systems allowed by theory require a nonlinear activation rate and a linear degradation rate. It is believed that the identified network defined in this study represents the minimal genetic components required for bistability of BMP signaling in D. melanogaster. In turn, bistability canalizes dorsal patterning. During amnioserosa specification, egr provides positive feedback, conferring nonlinearity, while cv-2> acts as a linear negative regulator of the signaling pathway. The loss of both components reveals the inherent noise of facilitated extracellular diffusion of BMP ligands, as without egr and cv-2, embryos manifest a huge range of signaling domain breadth and intensity. The data also reveal that amnioserosa specification in D. melanogaster is robust on multiple levels, with different mechanisms ensuring robustness in various Drosophila species (Gavin-Smith, 2013).

First, egr or bsk RNAi embryos have normal amounts of amnioserosa and minimal embryonic lethality despite the 2-fold reduction in signaling intensity. This demonstrates that amnioserosa specification is robust to decreases of BMP signaling and the wild-type level of BMP signaling in D. melanogaster is much higher than necessary. Second, the D. melanogaster embryo can tolerate at least a 250% increase or a 20% decrease in amnioserosa cell number without compromising viability. Lastly, the variability in amnioserosa cell number in D. yakuba embryos is equivalent to that in D. melanogaster embryos, indicating that amnioserosa specification in D. yakuba is robust against variable BMP signaling intensity. Therefore, in D. yakuba embryos, either less BMP signaling is required to direct amnioserosa specification or a second mechanism downstream of BMP signaling intensity maintains robust amnioserosa specification (Gavin-Smith, 2013).

Finally, as a counterpoint to the predicted ubiquity and selective maintenance of developmental canalization, D. santomea has been identified as a noncanalized wildtype species. D. santomea both has highly variable cell fate specification and is not robust to genetic variants found in its wild population. The identification of this noncanalized species may permit further investigation of the evolutionary factors allowing for this diversity in developmental trajectories (Gavin-Smith, 2013).


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zerknüllt: Biological Overview | Evolutionary Homologs | Regulation | Targets of Activity | Developmental Biology | Effects of Mutation

date revised: 22 October 2014 

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