In C. elegans, the anteroposterior polarities of a pair of cells in the tail, called TL and TR, are controlled by a WNT signal encoded by
lin-44. Mutations in
lin-44 cause the reversal of T cell polarity. Mutations in
lin-17, which encodes a Frizzled-like protein, cause the loss of T cell polarity, suggesting that LIN-17 is a receptor of the LIN-44 WNT signal. Other Wnt pathway components that have been shown to function in the control of T cell polarity include LIT-1/NLK, WRM-1/beta-catenin, SYS-1/beta-catenin and POP-1/TCF. As in many other anterior-posterior asymmetric cell divisions, the nuclear level of POP-1 is higher in the anterior T cell daughter, T.a, than it is in the posterior daughter, T.p. We have identified several mutations that define new genes involved in the control of T cell polarity, including
tcl-1. The
tcl-1 mutation causes the loss of neural cell fates in the T cell lineage and is incompletely penetrant. Genetic tests suggest that our
tcl-1 allele might cause a weak novel function. Analysis of T cell lineages revealed that T.p often fails to divide in
tcl-1 hermaphrodites. We also have determined that
tcl-1 affects distribution of GFP::POP-1 to the T cell daughters, thus TCL-1 functions early in the control of T cell polarity.
tcl-1 mutants also appear to have an additional defect affecting either the neurons or the supporting cells of the sensory phasmid in the tail. We have rescued
tcl-1 with cosmid F55A12, on which there are 10 candidate predicted genes. A genomic fragment that contained both F55A12.2 and
ppk-1 rescued
tcl-1 mutants, whereas a fragment containing only
ppk-1 did not. Furthermore, F55A12.2 is only 712 bp downstream of
ppk-1 and is trans-spliced to SL2, suggesting that these two genes are in an operon. Although, it is not yet clear which corresponds to
tcl-1 and how it might function in T cell asymmetry,
ppk-1 encodes a type I phosphatidylinosital phosphate kinase. These enzymes phosphorylate phosphatidylinositol 4-phosphate to generate phosphatidylinositol 4,5 bisphosphate (PI4, 5P2) that can modulate many cellular behaviors, including cell proliferation. Establishing a role for
ppk-1 in cellular asymmetry would be an important finding and could link cell signaling to cell polarity.