1. FGF signaling is required for chemokinesis and ventral migration of trunk neural crest cells.
- Author
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Dunkel H, Chaverra M, Bradley R, and Lefcort F
- Subjects
- Animals, Ganglia, Spinal cytology, Ganglia, Spinal metabolism, Mice, Neural Crest cytology, Receptor, Fibroblast Growth Factor, Type 1 metabolism, Cell Movement, Chemokines metabolism, Fibroblast Growth Factors metabolism, Neural Crest metabolism, Signal Transduction
- Abstract
Background: Neural crest cells (NCCs) delaminate from the neural tube (NT) and migrate ventrally to generate the trunk peripheral nervous system (PNS). Although several signaling pathways have been identified that steer NCCs once they are on their ventral trajectory, no molecules have been identified that are required for the initial migration between the NT and the dorsal root ganglion. Given the critical role of fibroblast growth factor (FGF) signaling in embryogenesis, we investigated its function in this initial migration., Results: FGFR1 signaling is required for the migration of newly delaminated NCCs onto the ventral pathway. Live imaging of migrating NCCs revealed that inhibition of FGFR1 signaling caused the dorsally stalled NCCs to lose their dorsal/ventral oriented polarity and instead adopt a rounded morphology while dynamically extending filopodia. FGF8, an FGFR1 ligand, increased motility of NCCs away from the NT by acting chemokinetically. Finally, we provide evidence that inhibition of FGFR1-mediated chemokinesis is partially rescued by increasing Akt signaling, inhibiting RhoA, and activation of N-cadherin signaling., Conclusion: These data support a model in which NCCs are stimulated chemokinetically by FGF:FGFR1 signaling, and that this activation positions and orients NCCs on their ventral migratory route-a process that is essential for patterning the trunk PNS., (© 2020 Wiley Periodicals, Inc.)
- Published
- 2020
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