IGF-1 receptor regulates dynamic changes in neuronal polarity during cerebral cortical migration

Abstract During cortical development, neurons undergo polarization, oriented migration and layer-type differentiation. The biological and biochemical mechanisms underlying these processes are not completely understood. In neurons in culture we showed that IGF-1 receptor activation is important for g...

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Autores principales:	Alvaro F. Nieto Guil, Mariana Oksdath, Linnea A. Weiss, Diego J. Grassi, Lucas J. Sosa, Marta Nieto, Santiago Quiroga
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4883c92662b045dda79d1eb15277e16a
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spelling	oai:doaj.org-article:4883c92662b045dda79d1eb15277e16a2021-12-02T16:06:41ZIGF-1 receptor regulates dynamic changes in neuronal polarity during cerebral cortical migration10.1038/s41598-017-08140-52045-2322https://doaj.org/article/4883c92662b045dda79d1eb15277e16a2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08140-5https://doaj.org/toc/2045-2322Abstract During cortical development, neurons undergo polarization, oriented migration and layer-type differentiation. The biological and biochemical mechanisms underlying these processes are not completely understood. In neurons in culture we showed that IGF-1 receptor activation is important for growth cone assembly and axonal formation. However, the possible roles of the insulin like growth factor-1 receptor (IGF-1R) on neuronal differentiation and polarization in vivo in mammals have not yet been studied. Using in utero electroporation, we show here that the IGF-1R is essential for neocortical development. Neurons electroporated with a shRNA targeting IGF-1 receptor failed to migrate to the upper cortical layers and accumulated at the ventricular/subventricular zones. Co-electroporation with a constitutively active form of PI3K rescued migration. The change of the morphology from multipolar to bipolar cells was also attenuated. Cells lacking the IGF-1 receptor remain arrested as multipolar forming a highly disorganized tissue. The typical orientation of the migrating neurons with the Golgi complex oriented toward the cortical upper layers was also affected by electroporation with shRNA targeting IGF-1 receptor. Finally, cells electroporated with the shRNA targeting IGF-1 receptor were unable to form an axon and, therefore, neuron polarity was absent.Alvaro F. Nieto GuilMariana OksdathLinnea A. WeissDiego J. GrassiLucas J. SosaMarta NietoSantiago QuirogaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alvaro F. Nieto Guil Mariana Oksdath Linnea A. Weiss Diego J. Grassi Lucas J. Sosa Marta Nieto Santiago Quiroga IGF-1 receptor regulates dynamic changes in neuronal polarity during cerebral cortical migration
description	Abstract During cortical development, neurons undergo polarization, oriented migration and layer-type differentiation. The biological and biochemical mechanisms underlying these processes are not completely understood. In neurons in culture we showed that IGF-1 receptor activation is important for growth cone assembly and axonal formation. However, the possible roles of the insulin like growth factor-1 receptor (IGF-1R) on neuronal differentiation and polarization in vivo in mammals have not yet been studied. Using in utero electroporation, we show here that the IGF-1R is essential for neocortical development. Neurons electroporated with a shRNA targeting IGF-1 receptor failed to migrate to the upper cortical layers and accumulated at the ventricular/subventricular zones. Co-electroporation with a constitutively active form of PI3K rescued migration. The change of the morphology from multipolar to bipolar cells was also attenuated. Cells lacking the IGF-1 receptor remain arrested as multipolar forming a highly disorganized tissue. The typical orientation of the migrating neurons with the Golgi complex oriented toward the cortical upper layers was also affected by electroporation with shRNA targeting IGF-1 receptor. Finally, cells electroporated with the shRNA targeting IGF-1 receptor were unable to form an axon and, therefore, neuron polarity was absent.
format	article
author	Alvaro F. Nieto Guil Mariana Oksdath Linnea A. Weiss Diego J. Grassi Lucas J. Sosa Marta Nieto Santiago Quiroga
author_facet	Alvaro F. Nieto Guil Mariana Oksdath Linnea A. Weiss Diego J. Grassi Lucas J. Sosa Marta Nieto Santiago Quiroga
author_sort	Alvaro F. Nieto Guil
title	IGF-1 receptor regulates dynamic changes in neuronal polarity during cerebral cortical migration
title_short	IGF-1 receptor regulates dynamic changes in neuronal polarity during cerebral cortical migration
title_full	IGF-1 receptor regulates dynamic changes in neuronal polarity during cerebral cortical migration
title_fullStr	IGF-1 receptor regulates dynamic changes in neuronal polarity during cerebral cortical migration
title_full_unstemmed	IGF-1 receptor regulates dynamic changes in neuronal polarity during cerebral cortical migration
title_sort	igf-1 receptor regulates dynamic changes in neuronal polarity during cerebral cortical migration
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4883c92662b045dda79d1eb15277e16a
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IGF-1 receptor regulates dynamic changes in neuronal polarity during cerebral cortical migration

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