Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation

Abstract Neural connectivity requires neuronal differentiation, axon growth, and precise target innervation. Midbrain dopaminergic neurons project via the nigrostriatal pathway to the striatum to regulate voluntary movement. While the specification and differentiation of these neurons have been exte...

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Autores principales:	Shane V. Hegarty, Sean L. Wyatt, Laura Howard, Elke Stappers, Danny Huylebroeck, Aideen M. Sullivan, Gerard W. O’Keeffe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9ee052d1ada741f9b85c91ca265a86f0
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spelling	oai:doaj.org-article:9ee052d1ada741f9b85c91ca265a86f02021-12-02T12:30:18ZZeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation10.1038/s41598-017-08900-32045-2322https://doaj.org/article/9ee052d1ada741f9b85c91ca265a86f02017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08900-3https://doaj.org/toc/2045-2322Abstract Neural connectivity requires neuronal differentiation, axon growth, and precise target innervation. Midbrain dopaminergic neurons project via the nigrostriatal pathway to the striatum to regulate voluntary movement. While the specification and differentiation of these neurons have been extensively studied, the molecular mechanisms that regulate midbrain dopaminergic axon growth and target innervation are less clear. Here we show that the transcription factor Zeb2 cell-autonomously represses Smad signalling to limit midbrain dopaminergic axon growth and target innervation. Zeb2 levels are downregulated in the embryonic rodent midbrain during the period of dopaminergic axon growth, when BMP pathway components are upregulated. Experimental knockdown of Zeb2 leads to an increase in BMP-Smad-dependent axon growth. Consequently there is dopaminergic hyperinnervation of the striatum, without an increase in the numbers of midbrain dopaminergic neurons, in conditional Zeb2 (Nestin-Cre based) knockout mice. Therefore, these findings reveal a new mechanism for the regulation of midbrain dopaminergic axon growth during central nervous system development.Shane V. HegartySean L. WyattLaura HowardElke StappersDanny HuylebroeckAideen M. SullivanGerard W. O’KeeffeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shane V. Hegarty Sean L. Wyatt Laura Howard Elke Stappers Danny Huylebroeck Aideen M. Sullivan Gerard W. O’Keeffe Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation
description	Abstract Neural connectivity requires neuronal differentiation, axon growth, and precise target innervation. Midbrain dopaminergic neurons project via the nigrostriatal pathway to the striatum to regulate voluntary movement. While the specification and differentiation of these neurons have been extensively studied, the molecular mechanisms that regulate midbrain dopaminergic axon growth and target innervation are less clear. Here we show that the transcription factor Zeb2 cell-autonomously represses Smad signalling to limit midbrain dopaminergic axon growth and target innervation. Zeb2 levels are downregulated in the embryonic rodent midbrain during the period of dopaminergic axon growth, when BMP pathway components are upregulated. Experimental knockdown of Zeb2 leads to an increase in BMP-Smad-dependent axon growth. Consequently there is dopaminergic hyperinnervation of the striatum, without an increase in the numbers of midbrain dopaminergic neurons, in conditional Zeb2 (Nestin-Cre based) knockout mice. Therefore, these findings reveal a new mechanism for the regulation of midbrain dopaminergic axon growth during central nervous system development.
format	article
author	Shane V. Hegarty Sean L. Wyatt Laura Howard Elke Stappers Danny Huylebroeck Aideen M. Sullivan Gerard W. O’Keeffe
author_facet	Shane V. Hegarty Sean L. Wyatt Laura Howard Elke Stappers Danny Huylebroeck Aideen M. Sullivan Gerard W. O’Keeffe
author_sort	Shane V. Hegarty
title	Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation
title_short	Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation
title_full	Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation
title_fullStr	Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation
title_full_unstemmed	Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation
title_sort	zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9ee052d1ada741f9b85c91ca265a86f0
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Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation

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