The tailless family of nuclear receptors is highly conserved among animals. The C. elegans tailless ortholog,
nhr-67, is expressed in a dynamic pattern in pre-uterine cells.
nhr-67 is initially expressed in the 4 pre-VU cells during the L2 stage, and subsequently expressed at higher levels in the anchor cell (AC) and lower levels in the VU cells, apparently in response to the
lin-12/lag-2 reciprocal signaling system. During the L3 stage,
nhr-67 expression is maintained at high levels in the AC and briefly at low levels in the six p cells whose twelve progeny form the UTSE and UV1 cells of the adult ventral uterus. Development of the p cells also depends on a
lin-12 - based signal from the AC. From the mid L4 stage through adulthood,
nhr-67 is expressed at low levels in the nuclei of the UTSE syncytium. In mutants homozygous for hypomorphic
nhr-67 promoter mutations that were identified by Bernard Lakowski''s laboratory, the development of the p cell descendants is defective by multiple criteria. In contrast, the AC appears normal during the L3 and early L4 stages, although it fails to fuse with UTSE in late L4 (likely due to the defective UTSE). The expression of
nhr-67 is downstream of
lin-12(RNAi) knockdown and
lin-12(gf) mutations in the AC and the p cells, and
nhr-67(lf) mutations are epistatic to
lin12(gf) mutations in the p cells. In
lag-1 (RNAi) L2 animals
nhr-67 is expressed at higher levels in both the presumptive AC and VU cells of animals. In
nhr-67(RNAi) L2 animals,
egl-43 is expressed at higher levels in both the presumptive AC and VU cells. Taken together, these data indicate that
nhr-67 is a component of the regulatory response to
lin-12 signaling in the VU and p cells. Possible null alleles that delete most of the
nhr-67 ligand-binding domain cause L1 arrest after hatching. Rare escapers are Pvl, Egl and Ste. The arrested L1 larvae display tail defects in the
hyp10 epithelial cell similar to those caused by mutations in the cadherin gene cdh 3, although expression of
cdh-3::gfp in tail hypodermal cells is not obviously altered in
nhr-67 mutants. This work was supported by a grant from the NSF.