Making worm guts: the gene regulatory network of the Caenorhabditis elegans endoderm.

The nematode Caenorhabditis elegans is a triploblastic ecdysozoan, which, although it contains too few cells during embryogenesis to create discernible germ "layers," deploys similar programs for germ layer differentiation used in animals with many more cells. The endoderm arises from a single progenitor, the E cell, and is selected from among three possible fates by a three-state combinatorial regulatory system involving intersecting cell-intrinsic and intercellular signals. The core gene regulatory cascade that drives endoderm development, extending from early maternal regulators to terminal differentiation genes, is characterized by activation of successive tiers of transcription factors, including a sequential cascade of redundant GATA transcription factors. Each tier is punctuated by a cell division, raising the possibility that intercession of one cell cycle round, or DNA replication, is required for activation of the next tier. The existence of each tier in the regulatory hierarchy is justified by the assignment of a unique task and each invariably performs at least two functions: to activate the regulators in the next tier and to perform one other activity distinct from that of the next tier. While the regulatory inputs that initiate endoderm development are highly divergent, they mobilize a gene regulatory network for endoderm development that appears to be common to all triploblastic metazoans. Genome-wide functional genomic approaches, including identification of >800 transcripts that exhibit the same regulatory patterns as a number of endoderm-specific genes, are contributing to elucidation of the complete endoderm gene regulatory network in C. elegans. Dissection of the architecture of the C. elegans endoderm network may provide insights into the evolutionary plasticity and origins of this germ layer.