The role of Wnt/planar cell polarity signaling in mouse facial branchiomotor neuron migration

Abstract

Neuronal migration is essential for the formation of distinct neural layers and functional neural networks in the developing central nervous system. As a model, we study the caudal migration of facial branchiomotor neurons (FBMNs) from rhombomere 4 (r4) to r6 within the developing mouse hindbrain. Since Wnt/planar cell polarity (PCP) signaling components had been implicated in zebrafish FBMN migration, we tested whether they also were required in mice. FBMNs failed to migrate caudally in Vangl2 (Looptail) mutants, Vangl2 knockout embryos, and Ptk7 mutants, indicating a specific role for Vangl2 and Wnt/PCP signaling in FBMN migration. However, FBMNs migrated normally in Dishevelled 1/2 double mutants and in zebrafish embryos with disrupted dishevelled signaling. These results suggest strongly that the caudal migration of FBMNs is controlled by multiple components of the Wnt/PCP pathway, yet may not require the central signaling molecule Dishevelled. Interestingly, in Celsr1 (Crash) mutants, many FBMNs migrated rostrally instead of caudally, indicating a specific role for Celsr1 in the directionality of FBMN migration. To better understand how Celsr1 functions, we inactivated Celsr1 in specific hindbrain tissues and found that it functions within the ventricular zone of rhombomeres 3 through 5 to regulate FBMN directionality. Using anterograde labeling with lipophilic dyes, we also found that the starting positions of individual FBMNs within r4 correlated with the direction of migration in Celsr1Crsh/+ mutants. Together, these results indicate that Celsr1 is required in the ventricular zone of multiple rhombomeres to regulate the direction of FBMN migration, and provides insight as to how only a subset of FBMNs is affected in Celsr1 mutants.