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Tcf7l2 is required for left-right asymmetric differentiation of habenular neurons.

Hüsken, U; Stickney, HL; Gestri, G; Bianco, IH; Faro, A; Young, RM; Roussigne, M; Hawkins, TA; Beretta, CA; Brinkmann, I; et al. Hüsken, U; Stickney, HL; Gestri, G; Bianco, IH; Faro, A; Young, RM; Roussigne, M; Hawkins, TA; Beretta, CA; Brinkmann, I; Paolini, A; Jacinto, R; Albadri, S; Dreosti, E; Tsalavouta, M; Schwarz, Q; Cavodeassi, F; Barth, AK; Wen, L; Zhang, B; Blader, P; Yaksi, E; Poggi, L; Zigman, M; Lin, S; Wilson, SW; Carl, M (2014) Tcf7l2 is required for left-right asymmetric differentiation of habenular neurons. Curr Biol, 24 (19). pp. 2217-2227. ISSN 1879-0445 https://doi.org/10.1016/j.cub.2014.08.006
SGUL Authors: Cavodeassi, Florencia

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Abstract

BACKGROUND: Although left-right asymmetries are common features of nervous systems, their developmental bases are largely unknown. In the zebrafish epithalamus, dorsal habenular neurons adopt medial (dHbm) and lateral (dHbl) subnuclear character at very different frequencies on the left and right sides. The left-sided parapineal promotes the elaboration of dHbl character in the left habenula, albeit by an unknown mechanism. Likewise, the genetic pathways acting within habenular neurons to control their asymmetric differentiated character are unknown. RESULTS: In a forward genetic screen for mutations that result in loss of habenular asymmetry, we identified two mutant alleles of tcf7l2, a gene that encodes a transcriptional regulator of Wnt signaling. In tcf7l2 mutants, most neurons on both sides differentiate with dHbl identity. Consequently, the habenulae develop symmetrically, with both sides adopting a pronounced leftward character. Tcf7l2 acts cell automously in nascent equipotential neurons, and on the right side, it promotes dHbm and suppresses dHbl differentiation. On the left, the parapineal prevents this Tcf7l2-dependent process, thereby promoting dHbl differentiation. CONCLUSIONS: Tcf7l2 is essential for lateralized fate selection by habenular neurons that can differentiate along two alternative pathways, thereby leading to major neural circuit asymmetries.

Item Type: Article
Additional Information: Copyright © 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
Keywords: Animals, Cell Differentiation, Embryo, Nonmammalian, Gene Expression Regulation, Habenula, Neurons, Signal Transduction, Transcription Factor 7-Like 2 Protein, Zebrafish, Zebrafish Proteins, Developmental Biology, 06 Biological Sciences, 11 Medical And Health Sciences, 17 Psychology And Cognitive Sciences
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: Curr Biol
ISSN: 1879-0445
Language: eng
Dates:
DateEvent
6 October 2014Published
4 September 2014Published Online
2 August 2014Accepted
Publisher License: Creative Commons: Attribution 3.0
Projects:
Project IDFunderFunder ID
MR/L003775/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
BB/H012516/1Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UNSPECIFIEDWellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 25201686
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109997
Publisher's version: https://doi.org/10.1016/j.cub.2014.08.006

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