What factors direct the transition from specification to differentiation during intestinal development in the nematode Caenorhabditis elegans?

Specification of the C. elegans endoderm

Specification of the C. elegans endoderm (E lineage) is directed by a transcriptional regulatory cascade that includes maternally provided SKN-1, its targets, the genes encoding the MED-1 and -2 GATA-like transcription factors, and their targets, the genes encoding the END-1 and -3 GATA factors.  The transition from endoderm specification to intestinal differentiation is mediated in part by the ELT-2 GATA transcription factor.

Current Research: Intestinal differentiation in the C. elegans embryo

Based on recent comprehensive SAGE analyses, McGhee and colleagues proposed that ELT-2 is the dominant regulator of intestinal differentiation, and that other GATA transcription factors expressed in the late developing intestine, ELT-7 and ELT-4, play at most a subsidiary role.  However, the intestines of elt-2(0) animals, while defective in function, are well-differentiated, and contain a well-developed brush border and rhabditin granules throughout.  The most striking phenotypes of elt-2(0) animals are larval lethality and an obstructed gut lumen that is otherwise clearly evident; in short, these mutants appear to undergo largely normal gut differentiation, implying that ELT-2 functions with other factors to direct gut differentiation.

A candidate for such a factor is ELT-7, which we found shows gut-specific expression at the appropriate time in development and whose expression is sufficient to activate gut differentiation when expressed outside of the E lineage.  Indeed, while elt-7(tm840)V mutants are essentially wild type, we found that intestinal differentiation is dramatically impaired in an elt-7(tm840)V;elt-2(ca15)X double mutant, and current efforts are focused on further characterizing the phenotype of these double mutants.