Our current model for T cell polarity suggests an instructive role for the LIN-44/Wnt signal that emanates from the tail tip cells and functions to polarize the T cells that are anterior to the source of the signal. In
lin-44 mutants the polarities of the T cells are reversed and in
lin-17 mutants the asymmetries of the T cell divisions are lost. This suggests the existence of a second signal emanating from an anterior source that in the absence of LIN-44/Wnt causes a reversal of T cell polarity.
lin-17 mutants lack a Wnt receptor and display a loss of polarity, suggesting that this putative second signal is a Wnt that also functions as an instructive signal.1 We have begun testing this "2 signal model" using a combination of zygotic and feeding RNAi of other C. elegans Wnt genes. Thus far, a candidate for the second signal has not been found. The search will continue using
rrf-3 mutants that are hypersensitive to RNAi and through RNAi of conserved Wnt pathway components, particularly MOM-1/Porc. LIN-44 may not function instructively, however. Initial experiments expressing
lin-44 from a heat shock promotor, presumably leading to uniform expression in many tissues, rescued the T cell polarity defect of
lin-44 mutants.2 This suggests that asymmetry of the signal may not be important for its function; thus it is a permissive signal. To determine whether LIN-44 functions instructively or permissively we have begun to test the ability of ectopically expressed LIN-44 to rescue the polarity defects of
lin-44 mutants. A
lin-44 cDNA expressed in the pharynx from the
myo-2 promotor did not rescue the T cell polarity defects of
lin-44 mutants. This suggests that either the pharynx is too far away from the T cell for LIN-44 to have an effect or that LIN-44 is not a permissive signal. We are confirming this result with a
myo-2::
lin-44::gfp construct using a GFP variant that is visible in extracellular spaces. Future experiments will include expression of
lin-44::gfp from other body regions closer to, but still anterior of, the T cell.1 Sawa et al. (1996) Genes Dev 10, 2189-97; 2 Herman et al. (1995) Cell 83, 101-10