During development, different cell fates are generated by asymmetric cell divisions and cell-cell interactions. The orientation of these cells to the body axis of an animal gives each cell a polarity. We are interested in how asymmetries are generated and how cell polarity is controlled during metazoan development. In some cases, the asymmetry of the daughter cells generated by an asymmetric division is apparent as a difference in cell size. The C. elegans male specific blast cell, B, divides asymmetrically to generate a large anterior-dorsal daughter (B.a) and a smaller posterior-ventral daughter (B.p).
lin-44/Wnt and
lin-17/Fz are involved in the control of B cell polarity. Mutations in
lin-44 cause a reversal of B cell polarity, while mutations in
lin-17 cause a symmetric B cell division.
lin-44 and
lin-17 also control the polarity of T cell, causing the reversal and loss of T cell polarity, respectively. A non-canonical Wnt pathway involved in planar cell polarity (PCP) has been described in both Drosophila and vertebrate systems. In Drosophila, epithelial cells in the eye, wing and thorax become polarized within the epithelial sheet by the action of the PCP pathway. The six PCP core genes, Fz, Dsh, Fmi, Pk, Stbm and Dgo, have been identified in Drosophila and their function and asymmetric distribution in the wing cells have been characterized. In addition, the PCP pathway plays an important role in the regulation of convergent extension movements during gastrulation in both zebrafish and Xenopus embryos. We have identified C. elegans PCP pathway homologs and used RNAi as well as available mutants to disrupt their functions to determine whether they are involved in the control of B cell polarity. We have found that disruption of
lin-44/Wnt,
lin-17/Fz,
mig-5/Dsh,
unc-44/Dgo,
rho-1/RhoA,
let-502/Rock and POP-1/Tcf functions cause B cell polarity defects, but with the exception of
lin-44 and
lin-17, do not cause T cell polarity defects. We have used double mutants analysis to determine that
rho-1 functions downstream of
lin-44. Our results suggest that components of the conserved PCP/Wnt pathway are involved in the control of B cell polarity. We are also performing a genetic screen for mutants that affect B cell polarity. We have already isolated one mutant,
mh52, which displays a high degree of B cell polarity reversals, but does not affect T cell polarity.
mh52 complements
lin-44 and
lin-17 mutants, suggesting that
mh52 defines a new gene involved in the control of B cell polarity. This is only the second gene that causes highly penetrant B cell reversals. Our long term goal is to determine how the new genes we identify function with the known PCP genes to control B cell polarity.