A novel role for MuSK and non-canonical Wnt signaling during segmental neural crest cell migration

Abstract

SUMMARYTrunk neural crest cells delaminate from the dorsal neural tube as an uninterrupted sheet; however, they convert into segmentally organized streams before migrating through the somitic territory. These neural crest cell streams join the segmental trajectories of pathfinding spinal motor axons, suggesting that interactions between these two cell types might be important for neural crest cell migration. Here, we show that in the zebrafish embryo migration of both neural crest cells and motor axons is temporally synchronized and spatially restricted to the center of the somite, but that motor axons are dispensable for segmental neural crest cell migration. Instead, we find that muscle-specific receptor kinase (MuSK) and its putative ligand Wnt11r are crucial for restricting neural crest cell migration to the center of each somite. Moreover, we find that blocking planar cell polarity (PCP) signaling in somitic muscle cells also results in non-segmental neural crest cell migration. Using an F-actin biosensor we show that in the absence of MuSK neural crest cells fail to retract non-productive leading edges, resulting in non-segmental migration. Finally, we show that MuSK knockout mice display similar neural crest cell migration defects, suggesting a novel, evolutionarily conserved role for MuSK in neural crest migration. We propose that a Wnt11r-MuSK dependent, PCP-like pathway restricts neural crest cells to their segmental path.

On the embryonic origin of adult melanophores: the role of ErbB and Kit signalling in establishing melanophore stem cells in zebrafish

“…MSCs require ErbB signalling and are associated with the DRGs Our live imaging confirms that NC migration along the ventromedial path occurs in close association with the extending primary motor axons (Banerjee et al, 2011). Melanoblasts of the larval pattern also migrate along this path, as shown by the direct tracing of mitfa:gfp cells that undergo melanisation (Fig.…”

Roles of Planar Cell Polarity Signaling in Maturation of Neuronal Precursor Cells in the Postnatal Mouse Olfactory Bulb

“…Roles of the Wnt/PCP pathway in cell migration have been reported in several different contexts [24][25][26][27][28][29][30][31][32]. In this work, blocking the Wnt/PCP pathway decreased the number of NPCs that reached the OB, without affecting their differentiation or proliferation (Figs.…”

“…Furthermore, the migration of facial branchiomotor (FBM) neurons [24][25][26][27][28][29][30][31] and neural crest cells [32] depends on the function of the PCP genes, as does neuronal morphogenesis in the postnatal hippocampus [33,34] and OB [35], indicating that PCP signaling is involved in the migration and differentiation of many types of neural cells [36][37][38]. However, the function of this signaling pathway in the postnatal migration and differentiation of neurons in the OB has not been clearly demonstrated.…”

The neural crest

“…Transient contacts between two colliding NC cells involve N-cadherin and lead to a local activation of the non-canonical Wnt/planar cell polarity (PCP) pathway, which in turn activates the small GTPase RhoA and inhibits Rac1, thus repolarising the cell. A role for Wnt/PCP in trunk NC cell migration has also been found in chick, zebrafish and mouse, but its connection with CIL has not been analysed (Banerjee et al, 2011;Rios et al, 2011).…”