Redundancy and the Recursive Feed-forward Architecture of Endodermal Gene Regulation in Caenorhabditis elegans.

摘要

Early developmental transitions, such as the specification-to-differentiation switch, are critical for successful embryogenesis in multi-cellular animals. For such transitions to occur regularly and robustly, each cell in the embryo must integrate an ensemble of inputs and then generate appropriate outputs that faithfully translate the many inputs despite transcriptional noise. Studies of endoderm development in the nematode worm C. elegans presented here demonstrate that a synergy of redundant partners is required both in the transition from specification to differentiation, which relies on redundant GATA factors END-1 (historically identified as a specification factor) and ELT-7 (a downstream differentiation factor) and at the initiation of differentiation, directed by redundant GATA factors ELT-7 and ELT-2. Subsequent study of the many instances of genetic redundancy found in endoderm development have revealed that the gene regulatory network directing intestinal fate may be best modeled as a recursive series of interlocking feed-forward modules. This model offers a satisfactory explanation for the pervasive theme of genetic redundancy observed in Caenorhabditis and provides a mechanism by which high fidelity is ensured in the invariant cell lineage of the rapidly developing C. elegans embryo.