Abstract
Collective migration depends on cell-cell interactions between neighbors that contribute to their overall directionality, yet the mechanisms that control the coordinated migration of neurons remains to be elucidated. During hindbrain development, facial branchiomotor neurons (FBMNs) undergo a stereotypic tangential caudal migration from their place of birth in rhombomere (r)4 to their final location in r6/7. FBMNs engage in collective cell migration that depends on neuron-to-neuron interactions to facilitate caudal directionality. Here, we demonstrate that Cadherin-2-mediated neuron-to-neuron adhesion is necessary for directional and collective migration of FBMNs. We generated stable transgenic zebrafish expressing dominant-negative Cadherin-2 (Cdh2ΔEC) driven by the islet1 promoter. Cell-autonomous inactivation of Cadherin-2 function led to non-directional migration of FBMNs and a defect in caudal tangential migration. Additionally, mosaic analysis revealed that Cdh2ΔEC-expressing FBMNs are not influenced to migrate caudally by neighboring wild-type FBMNs due to a defect in collective cell migration. Taken together, our data suggest that Cadherin-2 plays an essential cell-autonomous role in mediating the collective migration of FBMNs.
Highlights
Neuronal migration is a fundamental step in the assembly of neural circuits that control behavior
We show that Cadherin-2 is required cell autonomously in facial branchiomotor neurons (FBMNs) for sustained migration in the caudal direction
We found that expression of dominant-negative Cdh2 in FBMNs leads to random, non-directed migration, suggesting that Cdh2 is not required for motility, but promotes a coordinated caudal trajectory of FBMNs
Summary
Neuronal migration is a fundamental step in the assembly of neural circuits that control behavior. Neuron migration integrates multiple cellular and molecular events to coordinate movement from their birth place to their final destination. In contrast to radial migration in which neurons follow radial glial fibers, tangentially migrating neurons use interactions with other cell types to guide their movement. These interactions may be homotypic, in which a neuron relies on interactions with the same class of neurons, or heterotypic, in which interactions occur between other cell types in their environment to guide their trajectory. Collective cell migration, defined as the coordinated migration of cells, depends on cell-cell interactions between neighbors that contribute to their overall directionality[2,3,4].
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