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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| Format: | Article |
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eLife Sciences Publications Ltd
2019-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/47673 |
| _version_ | 1811252829706256384 |
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| author | Elif Kon Elisa Calvo-Jiménez Alexia Cossard Youn Na Jonathan A Cooper Yves Jossin |
| author_facet | Elif Kon Elisa Calvo-Jiménez Alexia Cossard Youn Na Jonathan A Cooper Yves Jossin |
| author_sort | Elif Kon |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T16:41:40Z |
| format | Article |
| id | doaj.art-a94ccd736ef4439fae277937e6eb81f6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:41:40Z |
| publishDate | 2019-10-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj.art-a94ccd736ef4439fae277937e6eb81f62022-12-22T03:24:46ZengeLife Sciences Publications LtdeLife2050-084X2019-10-01810.7554/eLife.47673N-cadherin-regulated FGFR ubiquitination and degradation control mammalian neocortical projection neuron migrationElif Kon0Elisa Calvo-Jiménez1Alexia Cossard2Youn Na3Jonathan A Cooper4https://orcid.org/0000-0002-8626-7827Yves Jossin5https://orcid.org/0000-0001-8466-7432Laboratory of Mammalian Development & Cell Biology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, BelgiumLaboratory of Mammalian Development & Cell Biology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, BelgiumLaboratory of Mammalian Development & Cell Biology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, BelgiumDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United StatesDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United StatesLaboratory of Mammalian Development & Cell Biology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, BelgiumThe 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.https://elifesciences.org/articles/47673cerebral cortexneuronal migrationFGFRembryogenesisubiquitindevelopment |
| spellingShingle | Elif Kon Elisa Calvo-Jiménez Alexia Cossard Youn Na Jonathan A Cooper Yves Jossin N-cadherin-regulated FGFR ubiquitination and degradation control mammalian neocortical projection neuron migration eLife cerebral cortex neuronal migration FGFR embryogenesis ubiquitin development |
| 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 | cerebral cortex neuronal migration FGFR embryogenesis ubiquitin development |
| url | https://elifesciences.org/articles/47673 |
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