The polarities of several cells that divide asymmetrically during C. elegans development are controlled by Wnt signaling. LIN-44/Wnt and LIN-17/Fz control the polarities of cells in the tail of developing C. elegans larvae, including the male-specific blast cell, B, that divides asymmetrically to generate a larger anterior daughter and a smaller posterior daughter. We determined that the three -catenin homologs, DSH-1/DSH-2/Dsh, APR-1/APC, SGG-1/GSK-3 and PRY-1/Axin are not involved in the control of B cell polarity. However, POP-1/Tcf is involved and asymmetrically distributed to B daughter nuclei. Aspects of the B cell division are reminiscent of the divisions controlled by the planar cell polarity (PCP) pathway that has been described in both Drosophila and vertebrate systems. We identified C. elegans homologs of Wnt/PCP signaling components and have determined that many of them appear to be involved in the regulation of B cell polarity and POP-1 asymmetric distribution to B daughter nuclei. Specifically, MIG-5/Dsh, RHO-1/RhoA and LET-502/ROCK appear to play major roles, while other PCP components appear to play minor roles. Thus a non-canonical Wnt pathway, which is different from other Wnt pathways in C. elegans, but similar to the PCP pathways, appears to regulate B cell polarity. Asymmetric localization of the six core PCP proteins, including Fz and Dsh, is required for PCP signaling. To determine whether LIN-17 and MIG-5 are asymmetrically localized during the B cell division, we constructed functional lin-17
::gfp and mig-5
::gfp fusion constructs. We determined that LIN-17 is localized to the B cell cortex and is asymmetrically distributed prior to, and after, division. Furthermore, during the B cell division the asymmetric localization of LIN-17::GFP was reversed in the lin-44
males. MIG-5::GFP is expressed in a punctate pattern in the B cell and is localized to the anterior cortex prior to B cell division. After the B cell division, MIG-5::GFP is asymmetrically distributed to the B daughter cells, with puncta localized at the posterior cortex of B.p cell as well as the interface between B.a and B.p. In lin-44
males, MIG-5::GFP puncta are localized to the anterior cortex of the B.a cell, instead of posterior cortex of the B.p cell as occurs in wild-type males. However in lin-17
males, the punctate expression pattern were not observed, suggesting that LIN-17 may be required for MIG-5 localization. We are currently examining the specificity of MIG-5 domains for localization and rescue of the mig-5
B cell polarity defects. In summary, a novel PCP-like pathway, in which LIN-17 and MIG-5 are asymmetrically localized, is involved in the regulation of B cell polarity.