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

iScience. 2019 May 31;15:257-273. doi: 10.1016/j.isci.2019.04.030. Epub 2019 Apr 26.

Mercurio S¹, Serra L², Motta A¹, Gesuita L¹, Sanchez-Arrones L³, Inverardi F⁴, Foglio B⁴, Barone C¹, Kaimakis P³, Martynoga B⁵, Ottolenghi S¹, Studer M⁶, Guillemot F⁵, Frassoni C⁴, Bovolenta P³, Nicolis SK⁷.

Author information

1. Department of Biotechnology and Biosciences, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy.
2. 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.
3. 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.
4. Clinical and Experimental Epileptology Unit, Fondazione I.R.C.C.S. Istituto Neurologico “Carlo Besta”, c/o AMADEOLAB, via Amadeo 42, 20133 Milano, Italy.
5. The Francis Crick Institute, Midland Road, London NW 1AT, UK.
6. Université Côte d’Azur, CNRS, Inserm, iBV, Nice, France.
7. Department of Biotechnology and Biosciences, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, Italy. Electronic address: silvia.nicolis@unimib.it.

Abstract

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.

PMID: 31082736
DOI: 10.1016/j.isci.2019.04.030