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Regulation of Neuronal Polarity by Wnt Signaling
AuthorJones, Kathleen Q.
AdvisorClark, Scott G.
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Wnts are highly conserved secreted glycoproteins that function in many developmental processes. Cell surface receptors, including the Frizzleds (Fz), ROR, and RYK families of proteins, bind Wnts to activate a number of downstream pathways. Wnts act redundantly to regulate the anteroposterior polarity of mechanosensory neurons ALM and PLM in C. elegans (Hilliard and Bargmann, 2006; Prasad and Clark, 2006). With the exception of one wnt/fz pair (lin-44/lin-17) the specific interactions between Wnt ligands and cell surface receptors in this process are unknown. A genetic screen was undertaken to identify genes that function in the pathway of either of two Wnts (egl-20 and cwn-1) known to determine ALM polarity. New alleles of cwn-1/wnt, lin-44/wnt and lin-17/fz were isolated as well as a mutation that affects both ALM and PLM polarity. Expression of PLR-1 in the mechanosensory neurons caused polarity defects indicating that Fz can influence their polarity. mom-5/fz RNAi generated polarity defects in both ALM and PLM supporting its involvement in this process. cfz-2/fz;lin-17 double mutants were found to enhance the ALN cell fate defects observed in lin-17 mutants. Finally the transgenic lines expressing PLR-1 in the mechanosensory neurons were crossed with cam-1 mutants enhancing the ALM defects in one line, and with lin-18 mutants attenuating the PLM polarity defects in both lines. This suggests that lin-18 and cam-1 might function in a signaling or regulatory capacity in ALM and PLM polarization.