During C. elegans development, cells throughout the embryo recognize a common anterior-posterior axis. Initial A-P polarity is established by sperm entry, and the par genes, but how is this polarity maintained during embryogenesis? A polarity inducing signal emanating out of the P2 blastomere is required for the polarity of the four cell stage blastomere EMS. EMS normally divides to produce an anterior daughter MS which produces primarily mesodermal tissue, and a posterior daughter E, which gives rise to intestine. Loss of this signal results in the posterior daughter E adopting an anterior MS cell fate, producing mesoderm in place of intestine. We have shown that this polarity inducing signal is complex involving distinct inputs from a Wnt signaling pathway (MOM-2 wnt signal and MOM-5 a frizzled receptor), and by an APC (adenomatous polyposis coli)-related gene, APR-1. These two inputs converge upon a b-catenin homolog WRM-1. WRM-1 functions to repress an HMG box protein POP-1. Antibody staining shows that POP-1 is found in the nucleus of the anterior cell MS at high levels and at low levels in the nucleus of the posterior cell E (Lin et al., 1995), and more recently that this staining pattern is the same many of the daughters of subsequent a-p divisions. This anterior POP-1 localization is dependent upon the MOM-2/MOM-5 signal and APR-1 (Lin et al., 1998). Currently we are using both forward and reverse genetics to identify new genes required for establishing and/or maintaining a-p polarity in the embryo. One very interesting gene defined by mutations but not yet cloned is
mom-4. Approximately 40% of
mom-4(
ne19) embryos fail to produce intestinal tissue. Genetic doubles between
mom-4 and
mom-2,
mom-5, or
apr-1, (which are also incompletely penetrant for the no gut phenotype), results in 100% penetrant no gut phenotypes. The
mom-4;
pop-1 doubles all exhibit the
pop-1 extra gut phenotype, indicating
mom-4 is upstream of
pop-1. The genetic interactions of
mom-4 with both the
mom-2/mom-5 and
apr-1 parallel inputs leaves no logical position for
mom-4 in the pathway. Interestingly
mom-4(
ne19); qDf9 animals produce dead embryos that all make intestine, indicating the MOM (more mesoderm) phenotype may not represent the null phenotype of the
mom-4 gene. Two genes
sgk-1(shaggy/GSK-3), and
src-1 have been identified that exhibit an extra gut defect, in which the extra gut is being produced by the P2 blastomere. Both
sgk-1 and
src-1 have been shown to genetically interact with
mom-2,
mom-5, and
apr-1 in a similar manner as does
mom-4 (see abstracts by Yanxia Bei and Jennifer Hogan). This data suggests that MOM-4 may function with SGK-1 and SRC-1 in regulating the polarity in EMS. Further genetic analysis, and cloning
mom-4 will be required to understand how MOM-4 may function.