Reelin/N-cadherin controls multipolar migration through FGFRs in the developing cerebral cortex
(2019)
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- Authors
- Supervisors
- Jossin, Yves
- Abstract
- The formation of the cerebral cortex depends on an extensive migration of future neurons away from their birth place to their final destination. Newly-born excitatory neurons migrate first as multipolar cells (slow and characterized by frequent changes in direction) then resume a bipolar migration (fast and unidirectional) to form what is called the cortical plate. The Reelin signaling pathway is important for cortical organization. The laboratory recently demonstrated that Reelin orients the multipolar neuronal migration towards the cortical plate by regulating Rap1 which in turn maintain N-Cadherin (NCad) at the cell surface. In this work, we show that NCad controls the multipolar migration through the activation of FGF receptors (FGFRs). NCad cell-autonomously binds FGFRs and inhibits FGFRs K27- and K29-linked polyubiquitination and lysosomal degradation. We found that Reelin, prevents FGFR degradation in a Rap1 and NCad-dependent manner and stimulates prolonged, FGFR-dependent, Erk1/2 phosphorylation. Accordingly, neurons inhibited for Erk1/2 do not migrate properly.
- Affiliations
Citations
Kon, E. (2019). Reelin/N-cadherin controls multipolar migration through FGFRs in the developing cerebral cortex. https://hdl.handle.net/2078.5/63098