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

Sara Mercurio , Linda Serra (1) , Alessia Motta , Lorenzo Gesuita , Luisa Sanchez-Arrones , Francesca Inverardi , Ben Foglio , Cristiana Barone , Polynikis Kaimakis , Ben Martynoga , Sergio Ottolenghi , Michele Studer (1) , François Guillemot , Carolina Frassoni , Paola Bovolenta , Silvia Nicolis , Benedetta Foglio

1 IBV - Institut de Biologie Valrose

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.

Mots clés: Biological Sciences; Developmental Neuroscience; Neuroscience

Domaines: Biologie du développement

Sara Mercurio, Linda Serra, Alessia Motta, Lorenzo Gesuita, Luisa Sanchez-Arrones, et al.. Sox2 Acts in Thalamic Neurons to Control the Development of Retina-Thalamus-Cortex Connectivity. iScience, 2019, 15, pp.257-273. ⟨10.1016/j.isci.2019.04.030⟩. ⟨hal-02189542⟩