Sox2 Acts in Thalamic Neurons to Control the Development of Retina-Thalamus-Cortex Connectivity.

Biological Sciences Developmental Neuroscience Neuroscience

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
31 May 2019
Historique:
received: 04 02 2019
revised: 05 04 2019
accepted: 23 04 2019
pubmed: 15 5 2019
medline: 15 5 2019
entrez: 15 5 2019
Statut: ppublish

Résumé

Visual system development involves the formation of neuronal projections connecting the retina to the thalamic dorso-lateral geniculate nucleus (dLGN) and the thalamus to the visual cerebral cortex. Patients carrying mutations in the SOX2 transcription factor gene present severe visual defects, thought to be linked to SOX2 functions in the retina. We show that Sox2 is strongly expressed in mouse postmitotic thalamic projection neurons. Cre-mediated deletion of Sox2 in these neurons causes reduction of the dLGN, abnormal distribution of retino-thalamic and thalamo-cortical projections, and secondary defects in cortical patterning. Reduced expression, in mutants, of Sox2 target genes encoding ephrin-A5 and the serotonin transport molecules SERT and vMAT2 (important for establishment of thalamic connectivity) likely provides a molecular contribution to these defects. These findings unveil thalamic SOX2 function as a novel regulator of visual system development and a plausible additional cause of brain-linked genetic blindness in humans.

Identifiants

pubmed: 31082736
pii: S2589-0042(19)30127-0
doi: 10.1016/j.isci.2019.04.030
pmc: PMC6517317
pii:
doi:

Types de publication

Journal Article

Langues

eng

Pagination

257-273

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Sara Mercurio (S)

Department of Biotechnology and Biosciences, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy.

Linda Serra (L)

Department of Biotechnology and Biosciences, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy; Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.

Alessia Motta (A)

Department of Biotechnology and Biosciences, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy.

Lorenzo Gesuita (L)

Department of Biotechnology and Biosciences, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy.

Luisa Sanchez-Arrones (L)

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid and CIBER de Enfermedades Raras (CIBERER), ISCIII Madrid, Madrid, Spain.

Francesca Inverardi (F)

Clinical and Experimental Epileptology Unit, Fondazione I.R.C.C.S. Istituto Neurologico "Carlo Besta", c/o AMADEOLAB, via Amadeo 42, 20133 Milano, Italy.

Benedetta Foglio (B)

Clinical and Experimental Epileptology Unit, Fondazione I.R.C.C.S. Istituto Neurologico "Carlo Besta", c/o AMADEOLAB, via Amadeo 42, 20133 Milano, Italy.

Cristiana Barone (C)

Department of Biotechnology and Biosciences, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy.

Polynikis Kaimakis (P)

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid and CIBER de Enfermedades Raras (CIBERER), ISCIII Madrid, Madrid, Spain.

Ben Martynoga (B)

The Francis Crick Institute, Midland Road, London NW 1AT, UK.

Sergio Ottolenghi (S)

Department of Biotechnology and Biosciences, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy.

Michèle Studer (M)

Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.

Francois Guillemot (F)

The Francis Crick Institute, Midland Road, London NW 1AT, UK.

Carolina Frassoni (C)

Clinical and Experimental Epileptology Unit, Fondazione I.R.C.C.S. Istituto Neurologico "Carlo Besta", c/o AMADEOLAB, via Amadeo 42, 20133 Milano, Italy.

Paola Bovolenta (P)

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid and CIBER de Enfermedades Raras (CIBERER), ISCIII Madrid, Madrid, Spain.

Silvia K Nicolis (SK)

Department of Biotechnology and Biosciences, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy. Electronic address: silvia.nicolis@unimib.it.

Classifications MeSH