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The Microtubule Regulator NEK7 Coordinates the Wiring of Cortical Parvalbumin Interneurons

Functional networks in the mammalian cerebral cortex rely on the interaction between glutamatergic pyramidal cells and GABAergic interneurons. Both neuronal populations exhibit an extraordinary divergence in morphology and targeting areas, which ultimately dictate their precise function in cortical...

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Detalles Bibliográficos
Autores principales: Hinojosa, Antonio Jesús, Deogracias, Rubén, Rico, Beatriz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6088228/
https://www.ncbi.nlm.nih.gov/pubmed/30067978
http://dx.doi.org/10.1016/j.celrep.2018.06.115
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author Hinojosa, Antonio Jesús
Deogracias, Rubén
Rico, Beatriz
author_facet Hinojosa, Antonio Jesús
Deogracias, Rubén
Rico, Beatriz
author_sort Hinojosa, Antonio Jesús
collection PubMed
description Functional networks in the mammalian cerebral cortex rely on the interaction between glutamatergic pyramidal cells and GABAergic interneurons. Both neuronal populations exhibit an extraordinary divergence in morphology and targeting areas, which ultimately dictate their precise function in cortical circuits. How these prominent morphological differences arise during development is not well understood. Here, we conducted a high-throughput screen for genes differentially expressed by pyramidal cells and interneurons during cortical wiring. We found that NEK7, a kinase involved in microtubule polymerization, is mostly expressed in parvalbumin (PV+) interneurons at the time when they establish their connectivity. Functional experiments revealed that NEK7-deficient PV+ interneurons show altered microtubule dynamics, axon growth cone steering and reduced axon length, arbor complexity, and total number of synaptic contacts formed with pyramidal cells. Altogether, our results reveal a molecular mechanism by which the microtubule-associated kinase NEK7 regulates the wiring of PV+ interneurons.
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spelling pubmed-60882282018-08-14 The Microtubule Regulator NEK7 Coordinates the Wiring of Cortical Parvalbumin Interneurons Hinojosa, Antonio Jesús Deogracias, Rubén Rico, Beatriz Cell Rep Article Functional networks in the mammalian cerebral cortex rely on the interaction between glutamatergic pyramidal cells and GABAergic interneurons. Both neuronal populations exhibit an extraordinary divergence in morphology and targeting areas, which ultimately dictate their precise function in cortical circuits. How these prominent morphological differences arise during development is not well understood. Here, we conducted a high-throughput screen for genes differentially expressed by pyramidal cells and interneurons during cortical wiring. We found that NEK7, a kinase involved in microtubule polymerization, is mostly expressed in parvalbumin (PV+) interneurons at the time when they establish their connectivity. Functional experiments revealed that NEK7-deficient PV+ interneurons show altered microtubule dynamics, axon growth cone steering and reduced axon length, arbor complexity, and total number of synaptic contacts formed with pyramidal cells. Altogether, our results reveal a molecular mechanism by which the microtubule-associated kinase NEK7 regulates the wiring of PV+ interneurons. Cell Press 2018-07-31 /pmc/articles/PMC6088228/ /pubmed/30067978 http://dx.doi.org/10.1016/j.celrep.2018.06.115 Text en Crown Copyright © 2018 Published by Elsevier Inc. All rights reserved. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hinojosa, Antonio Jesús
Deogracias, Rubén
Rico, Beatriz
The Microtubule Regulator NEK7 Coordinates the Wiring of Cortical Parvalbumin Interneurons
title The Microtubule Regulator NEK7 Coordinates the Wiring of Cortical Parvalbumin Interneurons
title_full The Microtubule Regulator NEK7 Coordinates the Wiring of Cortical Parvalbumin Interneurons
title_fullStr The Microtubule Regulator NEK7 Coordinates the Wiring of Cortical Parvalbumin Interneurons
title_full_unstemmed The Microtubule Regulator NEK7 Coordinates the Wiring of Cortical Parvalbumin Interneurons
title_short The Microtubule Regulator NEK7 Coordinates the Wiring of Cortical Parvalbumin Interneurons
title_sort microtubule regulator nek7 coordinates the wiring of cortical parvalbumin interneurons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6088228/
https://www.ncbi.nlm.nih.gov/pubmed/30067978
http://dx.doi.org/10.1016/j.celrep.2018.06.115
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