Abstract
Morphogenesis, the establishment of the animal body, requires the coordinated rearrangement of cells and tissues regulated by a very strictly-determined genetic program. Dorsal closure of the epithelium in the Drosophila melanogaster embryo is one of the best models for such a complex morphogenetic event. To explore the genetic regulation of dorsal closure, we carried out a large-scale RNA interference-based screen in combination with in vivo time-lapse microscopy and identified several genes essential for the closure or affecting its dynamics. One of the novel dorsal closure genes, the small GTPase activator pebble (pbl), was selected for detailed analysis. We show that pbl regulates actin accumulation and protrusion dynamics in the leading edge of the migrating epithelial cells. In addition, pbl affects dorsal closure dynamics by regulating head involution, a morphogenetic process mechanically coupled with dorsal closure. Finally, we provide evidence that pbl is involved in closure of the adult thorax, suggesting its general requirement in epithelial closure processes.
Highlights
Dorsal closure of the embryonic epithelium takes place during mid-embryogenesis, when two epithelial sheets migrate towards the dorsal midline where they meet and fuse [1]
We have identified novel dorsal closure genes involved in various biological processes, including small GTPase regulation, signal transduction, vesicle trafficking and embryonic patterning
In the ZCL0423 homozygous embryos, the GFP signal appeared after completion of germ band retraction in the dorsal-most epithelial (DME) cells and colocalized with the actin cables
Summary
Dorsal closure of the embryonic epithelium takes place during mid-embryogenesis, when two epithelial sheets migrate towards the dorsal midline where they meet and fuse [1]. Over the last few decades, several large-scale mutant screens have been performed to identify genes affecting embryonic morphogenesis [4,5,6] These classical genetic screens uncovered the roles of many genes in dorsal closure. Mutations of these genes led to the classical dorsal open phenotype: a hole in the larval cuticle. In addition to the signal transduction cascades, genes encoding structural elements of the cytoskeleton and the cell adhesion complexes have been identified as being involved in dorsal closure, based on the dorsal open phenotype of their mutations [8]. Genetic and cell biological analysis revealed the involvement of several regulators of the cytoskeleton in various stages of dorsal closure. Three GTPase regulators, the Rap activator PDZ-GEF, the Rac activator myoblast city and the Rac/cdc repressor rotund/racGAP84C, were identified as participating in the complex regulation of GTPase function in the embryonic epithelium undergoing dorsal closure [14,15,16]
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