The
nhr-67</I> gene encodes a conserved nuclear receptor that is the ortholog of the vertebrate TLX and Drosophila</I> 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</I> gene in C. elegans</I> result in early developmental arrest and death, indicating that
nhr-67</I> has an essential function. Arrested L1 larvae that lack
nhr-67</I> function display variable tail morphology defects, suggesting that
nhr-67</I> may play an evolutionarily-conserved role in posterior pattern formation. We have used RNAi and viable hypomorphic mutations isolated by Bernard Lakowskis laboratory (
pf2,
pf88</I>) to elucidate the role of
nhr-67</I> in the formation of the uterus. Nematodes that are compromised for
nhr-67</I> 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</I> expression,
nhr-67</I> is expressed in the uterine anchor cell (AC) during the L3 and early L4 stages, and more variably and briefly during L3 in the <font face=symbol>p</font> 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</I>, which functions in uterine development, in
nhr-67</I> mutants and found very little expression of
lin-11</I> in the uterine <font face=symbol>p</font> cells. We also examined the expression of
egl-13</I>, another transcriptional regulator involved in <font face=symbol>p</font> cell development, and found that expression was weaker than normal and the full complement of six <font face=symbol>p</font> cells per side was frequently not observed. Both UTSE and UV1 cells, the differentiated products of the twelve <font face=symbol>p</font> cells, are missing or highly abnormal in the
nhr-67</I> mutants. These data suggest that transcription of
egl-13</I>,
lin-11</I>, and other markers of proper <font face=symbol>p</font> cell differentiation depend on
nhr-67</I>, and suggest a potential pathway through which
nhr-67</I> regulates development of the ventral uterus. Analysis of
cdh-3::gfp</I> expression in the AC revealed no obvious defects in AC development, leaving open the question as to whether
nhr-67</I> plays an important role in AC function in uterine development. To clarify the role of
nhr-67</I>, we are investigating whether expression of
nhr-67</I> in the <font face=symbol>p</font> cells and AC depends on the
lag-2/lin-12</I> signaling pathway and whether the <font face=symbol>p</font> lineages are faithfully executed in
nhr-67</I> mutants.