Involvement of YAP-1, the Homolog of Yes-Associated Protein, in the Wnt-Mediated Neuronal Polarization in Caenorhabditis elegans

Guidance molecules, receptors, and downstream signaling pathways involved in the asymmetric neuronal cell migration and process outgrowth have been identified from genetic studies using model organisms, most of which are evolutionarily conserved. In the nematode Caenorhabditis elegans, the roles of Wnt ligands and their receptors in the polarization of specific sets of neurons along the anterior-posterior (A-P) body axis have been well elucidated, but their downstream effectors are relatively unknown. Here, we report yap-1, encoding an evolutionarily conserved transcriptional co-activator, as a novel player in the Wnt-mediated asymmetric development of specific neurons in C. elegans. We found that the loss of yap-1 activity failed to restrict the dendritic extension of ALM neurons to the anterior orientation, which is similar to the phenotype caused by defective cwn-1 and cwn-2 Wnt gene activities. Cell-specific rescue experiments showed that yap-1 acts in the cell autonomous manner to polarize ALM dendrites. We also found that subcellular localization of YAP-1 was spatio-temporally regulated. The loss of yap-1 in Wnt-deficient mutants did not increase the severity of the ALM polarity defect of the mutants. Wnt-deficient animals displayed abnormal subcellular localization of YAP-1 in touch receptor neurons, suggesting that yap-1 may act downstream of the cwn-1/cwn-2 Wnt ligands for the ALM polarization process. Together, we have identified a new role for YAP-1 in neuronal development and our works will contribute to further understanding of intracellular events in neuronal polarization during animal development.