CEMO monthly seminar - Elif Kon

CEMO is delighted to announce the seminars of the department that will be given by PhD student and Postdoc.

Agenda:

12:00: Reelin/N-cadherin Controls Multipolar Migration through FGFRs in the Developing Cerebral Cortex - Elif Kon

The functions of fibroblast growth factors (FGFs) and FGF receptors (FGFRs) in early development of the cerebral cortex are well established. Their functions in the migration of neocortical projection neurons, however, are unclear. We have found that FGFR 1, 2 and 3 regulate multipolar neuron orientation and the morphological change into bipolar cells necessary to enter the cortical plate. Mechanistically, our results suggest that FGFRs are activated by N-Cadherin. N-Cadherin cell-autonomously binds FGFRs and inhibits FGFR K27- and K29-linked polyubiquitination and lysosomal degradation. As a consequence, FGFRs accumulate and stimulate prolonged Erk1/2 phosphorylation. Neurons inhibited for Erk1/2 are stalled in the multipolar zone. We found that Reelin, prevents FGFR degradation in an N-Cadherin-dependent manner and stimulates prolonged, FGFR-dependent, Erk1/2 phosphorylation. These findings reveal novel functions for FGFRs in neuronal migration, suggest a physiological role for FGFR and N-Cadherin interaction in vivo and identify Reelin as an extracellular upstream regulator and Erk1/2 as downstream effectors of FGFRs during neuron migration.