To better understand the process by which cell polarity is established, we are analyzing genes required for the characteristic asymmetries of the early C. elegans embryo. Recently, we showed that the
pod-1 locus represents a new class of polarity genes as mutation of pod loci results in osmosensitive embryos in addition to loss of polarity ('pod'=polarity and osmotic defective). The identification of
pod-2 by our lab (see abstract by A. Tagawa) further underscores the importance of the pod class of mutants. The osmosensitivity of pod mutants appears to result from permeability of the egg shell surrounding the embryo. Understanding the connection between polarity establishment and egg shell formation should begin to reveal the molecular mechanisms underlying cellular asymmetry. To further identify the set of components responsible for this aspect of polarity establishment, we have initiated a study of mutants that have osmosensitive phenotypes. Among previously identified osmotically sensitive mutants,
emb-8 and
emb-30 mutants also exhibit the 'Pod' phenotype. In these, as well as a
pod-1 null mutant, the polarity defect is not completely penetrant suggesting that multiple, parallel pathways might contribute to overall cell polarity. However, analysis of double mutants between
pod-1 and
emb-8 or
emb-30 indicate that these three function in a common genetic pathway. Through two different genetic screens, one of which directly identifies osmosensitive embryos, we have isolated a number of other mutations that represent new loci of the pod class. This collection includes genes which when mutated cause near 100% penetrant loss of polarity. We are currently pursuing the molecular identities of these loci which will enable us to refine our models for how cellular asymmetry is controlled.