In C.elegans, as in other animals, the Wnt signaling pathway plays an important role in controlling cell polarities and cell migrations. For example,
lin-44/Wnt and
lin-17/Frizzled control the asymmetric divisions of T cells in the C. elegans tail.
lin-44 and
lin-17 also regulate the asymmetric distribution of POP-1/Tcf, a transcriptional regulator of Wnt signaling. In wild type animals, the anterior T cell daughter, T.a, has a higher POP-1 nuclear level than does the posterior daughter, T.p. Mutations in
lin-44 cause a reversal of T cell polarity and a corresponding reversal in POP-1 nuclear levels, such that T.a has a lower POP-1 nuclear level and T.p has a higher POP-1 nuclear level. Mutations in
lin-17 cause a loss of T cell polarity and equally high POP-1 nuclear levels in both the T.a and T.p cells, suggesting that
pop-1 functions after
lin-44 and
lin-17. We have isolated a mutant defining the new gene,
tcl-3(
mh32), that controls the asymmetric division of T cell.
tcl-3(
mh32) complements all known genes that affect T cell polarity, indicating that
tcl-3(
mh32) defines a new gene.
tcl-3(
mh32) is a recessive mutation and causes 66.4% (n=64) of T cell divisions to be defective. Examination of T cell descendants indicated that most often four hypodermal cells were generated, suggesting a loss of T cell polarity. Staining with POP-1 antibodies showed that POP-1 nuclear levels were equally high in both T.a and T.p cells in 56 % of
tcl-3(
mh32) mutants (n=54). This pattern of POP-1 nuclear distribution is similar to that observed in
lin-17 mutants, suggesting that
tcl-3 also functions before
pop-1 in the control of T cell division. Genes that affect T cell polarity, such as
lin-44,
lin-17,
tlp-1 and
tcl-2 often also regulate other cell fate specifications. For example, mutations in
lin-17 and
tcl-2 cause defects in B cell polarity, P11/P12 cell fate specification, gonad development and vulva development. In contrast to these mutants,
tcl-3 mutants do not display a B cell polarity defect nor a P11/P12 cell fate defect, indicating that
tcl-3 may not be involved in multiple cell fate decisions. We have used snip-SNP mapping to localize
tcl-3 to a small interval on the right arm of LGX. We are cloning and further characterizing
tcl-3 gene in order to understand its role in the control of the T cell polarity.