Regulation of Neuronal Polarity by Wnt Signaling

Abstract

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.