Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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

Hegarty, Shane V., Wyatt, Sean ORCID: https://orcid.org/0000-0002-0572-234X, 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

[thumbnail of Zeb2_is_a_negative_regulator_of_midbrain_dopaminer.pdf]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (9MB) | Preview

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: 03 May 2023 22:14
URI: https://orca.cardiff.ac.uk/id/eprint/104286

Citation Data

Cited 13 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics