Morphological features characterize every animal species and their study had major impacts for the formulation of concepts in biology. Paradoxically, the mechanisms underlying the acquisition of animal forms during development, as well as their diversification during evolution, remain poorly understood. Numerous functional studies have demonstrated that regulatory networks play critical roles in cell specification and differentiation and thereby control morphogenesis during development. It is well established that gene regulatory networks are implemented by transcription factors that bind to cis-regulatory elements to regulate gene expression. However our understanding of the fine structure and logic of these networks is currently limited to a few cases and mostly remain unconnected to morphological differentiation.
Therefore, a major challenge resides in deciphering the logic underlying developmental regulatory networks that are directly connected with evolutionary diversification.
We address this question through the analysis of a transcription factor, Shavenbaby, which controls a simple morphological trait during Drosophila development and was shown to underlie parallel evolution in insects. We have demonstrated that Shavenbaby directly controls the transcription of various cellular effectors, collectively responsible for the cell shape changes underlying epidermal differentiation and thus external morphology. Modifications of the cis-regulatory elements directing shavenbaby transcription have caused the morphological evolution that characterizes sibling Drosophila species. Shavenbaby expression integrates various developmental inputs, including those emanating from the well know regulatory networks underlying embryonic segmentation, dorso-ventral patterning, as well as Hox genes. Therefore, elucidation of the mechanisms acting upstream and downstream of shavenbaby will offer the opportunity to connect upstream regulatory cascades to the effectors of cell shape control.
Our goal is to provide a comprehensive understanding of this gene regulatory network and define functional consequences of its modifications across species. Our strategy is based on an integrated approach taking advantage of recent advances of genomic tools and knowledge in flies. It incorporates functional genomics, genome-wide identification of cis-regulatory elements from experimental and computational methods, and high throughput in vivo analyses.