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

Hegarty, Shane V., Wyatt, Sean, Howard, Laura, Stappers, Elke, Huylebroeck, Danny, Sullivan, Aideen M. and O'Keeffe, Gerard W. 2017. Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation. Scientific Reports 7 (1) , 8568. 10.1038/s41598-017-08900-3

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 4 September 2017
Date of Acceptance: 14 July 2017
Last Modified: 15 Jan 2018 11:03
URI: http://orca.cf.ac.uk/id/eprint/104286

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