Regulation of Neuronal Polarity by Wnt Signaling
AuthorJones, Kathleen Quinn
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 ,<italic>wnt/fz</italic> pair (<italic>lin-44/lin-17</italic>) 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 (<italic>egl-20</italic> and <italic>cwn-1</italic>) known to determine ALM polarity. New alleles of <italic>cwn-1/wnt, lin-44/wnt</italic> and <italic>lin-17/fz</italic> 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. <italic>mom-5/fz</italic> RNAi generated polarity defects in both ALM and PLM supporting its involvement in this process. <italic>cfz-2/fz; lin-17</italic> double mutants were found to enhance the ALN cell fate defects observed in <italic>lin-17</italic> mutants. Finally the transgenic lines expressing PLR-1 in the mechanosensory neurons were crossed with <italic>cam-1</italic> mutants enhancing the ALM defects in one line, and with <italic>lin-18</italic> mutants attenuating the PLM polarity defects in both lines. This suggests that <italic>lin-18</italic> and <italic>cam-1</italic> might function in a signaling or regulatory capacity in ALM and PLM polarization.