We are interested in how cell polarity is controlled during metazoan 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 three genes:
lin-44,
lin-17 and
egl-27 have previously been found to affect the polarity of certain cells in the tail called TL and TR.
lin-44 encodes 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 the more anterior T cells.
lin-17 encodes a putative WNT receptor and
egl-27 encodes a protein similar to a metastasis-associated factor, MTA1, and has been shown to be required within the T cells for normal polarity. We screened for additional mutants that affect T cell polarity to identify new genes that may interact with the genes known to control T cell polarity. We screened approximately 45,000 haploid genomes and isolated three new mutants:
mh15,
mh17 and
mh21. A fourth mutation,
mn593, was isolated in a preliminary screen of this type (see abstract by K. Williams and M. A. Herman). All three mutations are recessive and have been mapped to distinct intervals on LG IV. Phenotypic analyses indicate that
mh15 and
mh21 mutants display more severe T cell defects than do
mh17 mutants. In addition, all three mutations cause males to have abnormal tail morphologies. Some
mh15 and
mh17 male tails appear to have fused rays. The T cell division pattern is defective in these mutants. Cell lineage analysis of
mh15 indicates that several T cell daughters fail to divide and cell fates are not properly specified. These observations are consistent with a defect in T cell polarity. We are further analyzing the phenotypes of all three mutants and attempting to clone these genes by microinjection of relevant cosmid and YAC clones.