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

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...

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Autores principales: Kon, Elif, Calvo-Jiménez, Elisa, Cossard, Alexia, Na, Youn, Cooper, Jonathan A, Jossin, Yves
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786859/
https://www.ncbi.nlm.nih.gov/pubmed/31577229
http://dx.doi.org/10.7554/eLife.47673
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author Kon, Elif
Calvo-Jiménez, Elisa
Cossard, Alexia
Na, Youn
Cooper, Jonathan A
Jossin, Yves
author_facet Kon, Elif
Calvo-Jiménez, Elisa
Cossard, Alexia
Na, Youn
Cooper, Jonathan A
Jossin, Yves
author_sort Kon, Elif
collection PubMed
description 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.
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spelling pubmed-67868592019-10-15 N-cadherin-regulated FGFR ubiquitination and degradation control mammalian neocortical projection neuron migration Kon, Elif Calvo-Jiménez, Elisa Cossard, Alexia Na, Youn Cooper, Jonathan A Jossin, Yves eLife Developmental Biology 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. eLife Sciences Publications, Ltd 2019-10-02 /pmc/articles/PMC6786859/ /pubmed/31577229 http://dx.doi.org/10.7554/eLife.47673 Text en © 2019, Kon et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Kon, Elif
Calvo-Jiménez, Elisa
Cossard, Alexia
Na, Youn
Cooper, Jonathan A
Jossin, Yves
N-cadherin-regulated FGFR ubiquitination and degradation control mammalian neocortical projection neuron migration
title N-cadherin-regulated FGFR ubiquitination and degradation control mammalian neocortical projection neuron migration
title_full N-cadherin-regulated FGFR ubiquitination and degradation control mammalian neocortical projection neuron migration
title_fullStr N-cadherin-regulated FGFR ubiquitination and degradation control mammalian neocortical projection neuron migration
title_full_unstemmed N-cadherin-regulated FGFR ubiquitination and degradation control mammalian neocortical projection neuron migration
title_short N-cadherin-regulated FGFR ubiquitination and degradation control mammalian neocortical projection neuron migration
title_sort n-cadherin-regulated fgfr ubiquitination and degradation control mammalian neocortical projection neuron migration
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786859/
https://www.ncbi.nlm.nih.gov/pubmed/31577229
http://dx.doi.org/10.7554/eLife.47673
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