The E founder cell is the sole progenitor of the endoderm in the C. elegans embryo, giving rise exclusively to the 20 cells of the intestine. While several maternal pathways, and their zygotic gene targets, have been shown to specify the identity of the E cell, and many other genes are known to be expressed later in the developing gut, the precise genetic events that cause descendants of the E cell to differentiate into a functional organ are not yet understood. In an effort to understand the regulatory network of factors involved in gut formation, we are investigating the GATA-type transcription factor ELT-7. Previous work identified a number of GATA factors involved in C. elegans endoderm development. A pair of redundant GATA factors, MED-1 and -2, acts zygotically to specify the identity of EMS, the mother of E. The redundant END-1 and END-3 GATA factors in turn specify the identity of the E cell. Eliminating the function of both end genes, but not either alone, results in a penetrant E to C transformation and loss of the gut.
end-1::gfp and
end-3::gfp are expressed for only a brief period, from shortly after the time that E is born until the 8E cell stage. At the 2E cell stage, immediately after the end genes are activated, another GATA factor,
elt-2 , becomes expressed; however, unlike the end s,
elt-2 expression persists throughout the life of the animal. Elimination of ELT-2 results in a gut that degrades upon hatching, causing L1 lethality (Fukushige, et al., 1998). ELT-2 was identified by virtue of its interaction with GATA binding sites that are essential for wild-type expression of the gene encoding a gut-specific esterase,
ges-1 (Hawkins and McGhee, 1995). However,
elt-2 is not essential for
ges-1 expression, suggesting that it, and perhaps many other aspects of gut differentiation, is activated by a genetically redundant mechanism. We have identified a candidate redundant partner of ELT-2, the ELT-7 GATA factor. An
elt-7 reporter construct reveals an expression pattern that is indistinguishable from that of
elt-2 . Moreover, like the end genes and
elt-2 , ectopic
elt-7 is sufficient to promote widespread gut differentiation. While
elt-2(0) animal show a gut defect, RNAi of
elt-7 results in morphologically normal animals and
elt-7(RNAi) does not appear to enhance the degenerated gut phenotype of an
elt-2 mutant. However, partial elimination of
elt-2 and
elt-7 function by RNAi results in greatly diminished expression of a
ges-1::gfp reporter. This observation, the similar expression patterns of
elt-2 and -7 , and the genetic redundancy seen with the med , end , and other GATA factor-encoding genes (see abstract by Koh et al.), lead one to speculate that a similar redundant relationship might exist between
elt-2 and
elt-7 . We are in the process of examining the relationship between
elt-7 ,
elt-2 , and the end genes by ectopic expression experiments, RNAi, and "nuclear spot" assays to examine how the network of GATA factors functions to regulate differentiation of the gut. Fukushige, T., Hawkins M. G., McGhee, J, D. (1998) The GATA Factor
elt-2 is Essential for Formation of the Caenorhabditis elegans Intestine. Dev. Biol. 198 , 286-302. Hawkins, M. G., McGhee, J. D. (1995)
elt-2 , a Second GATA Factor from the Nematode Ceanorhabditis elegans . J. Biol. Chem. 270 , 14666-14671.