N-cadherin-regulated FGFR ubiquitination and degradation control mammalian neocortical projection neuron migration

eLife

Youn Na¹  Jonathan A Cooper¹  Elif Kon²  Alexia Cossard²  Elisa Calvo-Jiménez²  Yves Jossin² 

[1] Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States;Laboratory of Mammalian Development & Cell Biology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium;

关键词: cerebral cortex;    neuronal migration;    FGFR;    embryogenesis;    ubiquitin;    development;   

DOI  :  10.7554/eLife.47673

来源: DOAJ

【 摘 要 】

The functions of 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 FGFRs 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. Accordingly, FGFRs accumulate and stimulate prolonged Erk1/2 phosphorylation. Neurons inhibited for Erk1/2 are stalled in the multipolar zone. Moreover, Reelin, a secreted protein regulating neuronal positioning, prevents FGFR degradation through N-Cadherin, causing Erk1/2 phosphorylation. These findings reveal novel functions for FGFRs in cortical projection neuron 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.

【 授权许可】

Unknown