The E lineage is specified by the combined action of the maternal Wnt pathway and maternal SKN-1. These factors regulate E-specific expression of
end-1 and
end-3 , GATA factor-encoding genes expressed during a short interval (E 2 to E 8 cell stage). To elucidate the maternal control of these zygotic genes, we are investigating elements and factors that regulate
end-1 . The
end-1 regulatory region appears to be modularized, with a cluster of SKN-1 binding sites in a distal region (region III), a more proximal region (region II) containing elements conserved between
end-1 ,
end-3 , and the C. briggsae
end-1 , and a proximal-most region (region I) containing putative Wnt pathway-responsive elements, including a site resembling the consensus site for Lef-1, the target of the Wnt pathway. While regions II and III appear to enhance
end-1 expression, the 264 bp most proximal portion of region I confers proper spatial and temporal expression of
end-1 . Within region I, a 49 bp interval is essential for repression in non-E lineages and presumably identifies a target for a repressor acting outside of the E lineage. Just proximal is a 54 bp segment (region Ib), containing the apparent Wnt-responsive elements, which we find is essential for
end-1 expression in all lineages. The Wnt pathway in C. elegans was thought to act negatively, i.e., by inhibiting the Lef-1-like POP-1 protein, which represses endoderm development in the MS lineage. Our results suggest that Wnt-affected POP-1 may also activate
end-1 and endoderm development. Indeed, while depletion of maternal POP-1 derepresses endoderm and
end-1 expression in the MS lineage, it strongly enhances the impenetrant gutless phenotype of
skn-1(-) , demonstrating a positive role for POP-1 in endoderm specification. Thus, the Wnt signal apparently acts both to inhibit the MS-repressive activity of POP-1, and to cause POP-1 to be a transcriptional activator of the end genes in the E lineage. Both the repressive and activating functions of POP-1 may act through the Lef-1 site in region Ib of
end-1 . We have found that early embryonic extracts bind to region Ib in interactions that depend on the Lef-1 consensus site (see also abstract by Witze et al.).