We are interested in how cell polarity is controlled during C. elegans development. Our approach is to identify and study genes involved in the control of cell polarity by identifying mutations that disrupt the polarities of individual cells. Mutations in
lin-44 cause the polarities of certain cells in the tail, called TL and TR, to be reversed with respect to the body axis. LIN-44 is a WNT signaling protein that is made by the skin cells at the tip of the developing tail and functions to specify the polarity of more anterior tail cells. Mutations in
lin-17 and
egl-27 cause the loss of TL and TR cell polarities. LIN-17 is a Frizzled-like protein, suggesting that it is a receptor of LIN-44 WNT signal. EGL-27 contains a domain similar to MTA1, recently shown to be a sub-unit of a complex with chromatin-remodeling and histone deacetylase activities, and is required in the T cells for proper cell polarity. We want to learn how LIN-44 WNT signal from the tail skin cells influences the polarities of the receiving cells. The defects in T cell polarity observed in
lin-44,
lin-17 and
egl-27 mutants cause the two neurons of the phasmid, a sensory structure in the tail, to fail to fill with fluorescent dyes, FITC or DiO. New genes that may interact with
lin-44,
lin-17 and
egl-27 were identified by screening for additional mutations that result in a phasmid dye-filling defect caused by defects in T cell polarity. We are currently studying
tcl-1(
mn593), (T cell lineage defective) a new gene defined by a mutation isolated by Claire Kari in a preliminary screen of this type. Subsequent screens have identified at least three other new mutations affecting T cell polarity (see Abstracts by X. Zhao and T. Ratliff).
tcl-1 mutants display a partially penetrant phasmid dye-filling defect due, in part, to a T cell lineage defect; the posterior T cell daughter often fails to divide. We used the lipophilic fluorescent dye, di-4 ANEPPS, which preferentially fills functional phasmid socket cells, to determine that the remainder of the
tcl-1 phasmids that fail to fill with DiO, have functional phasmid socket cells. This suggests that there may be a phasmid neuron defect in some
tcl-1 animals. In addition,
tcl-1 males have abnormal tail morphologies, with sensory ray structures often fused or missing in rays descending from the V5 and V6 cells. Thus,
tcl-1 mutants appear to have defects in T cell polarity as well as other aspects of tail development. We have mapped
tcl-1 to the interval between
dpy-5 and
unc-63 on LG1. We are currently in the process of cloning
tcl-1 by microinjection of the relevant cosmid and YAC clones into
tcl-1 hermaphrodites.