The
nhr-67 gene encodes a conserved nuclear receptor that is the ortholog of the vertebrate TLX and Drosophila TLL genes. In vertebrates, TLX functions in nervous system development. In flies, TLL functions in nervous system development and anterior-posterior pattern formation. Deletions of the
nhr-67 gene in C. elegans result in early developmental arrest and death, indicating that
nhr-67 has an essential function. We have used RNAi and hypomorphic mutations isolated by Bernard Lakowski"s laboratory (
pf2,
pf88) to elucidate the role of
nhr-67 in the formation of the uterus. Nematodes that are compromised for
nhr-67 function display several phenotypes, including Unc, difficulty shedding the cuticle, Egl, and Pvl. The latter two phenotypes may be caused by defects in uterine and/or vulval development. Based on our analysis of
nhr-67::gfp expression,
nhr-67 is expressed in the uterine anchor cell (AC) and a subset of the π cells of the ventral uterus. Both of these cell types play critical roles in the formation of the ventral side of the uterus, which connects directly to the dorsal vulval cells. We examined the expression of the LIM homeobox gene
lin-11, which functions in uterine development, in
nhr-67(
pf2) mutant nematodes and found very little expression of
lin-11 in the uterine π cells. We also examined the expression of
egl-13, another transcriptional regulator involved in π cell development, and found that expression was often weaker than normal and the full complement of six π cells per side was not always observed. In later stage animals, we sometimes observed apparently normal UV1 cells, but very rarely observed UTSE cells that appeared normal, suggesting that UTSE is more severely affected than UV1. These data suggest that
egl-13 and
lin-11 transcription depend on
nhr-67, and suggest a potential pathway through which
nhr-67 regulates uterine development. Analysis of
cdh-3::gfp expression in the AC revealed no obvious defects in AC development. To clarify the role of
nhr-67, we will perform immunofluorescence experiments to determine if the
nhr-67(
pf2) and
nhr-67(
pf88) mutations disrupt
nhr-67 expression in the uterus as expected, and to determine the complete
nhr-67 expression pattern in wild-type animals.