SOX2 is a transcription factor conserved throughout vertebrate evolution, whose expression marks the central nervous system from the earliest developmental stages. In humans, SOX2 mutation leads to a spectrum of CNS defects, including vision and hippocampus impairments, in-tellectual disability, and motor control problems. Here, we review how conditional Sox2 knockout (cKO) in mouse with different Cre recombinases leads to very diverse phenotypes in different regions of the developing and postnatal brain. Surprisingly, despite the widespread expression of Sox2 in neural stem/progenitor cells of the developing neural tube, some regions (hippocampus, ventral forebrain) appear much more vulnerable than others to Sox2 deletion. Furthermore, the stage of Sox2 deletion is also a critical determinant of the resulting defects, pointing to a stage-specificity of SOX2 function. Finally, cKOs illuminate the importance of SOX2 function in different cell types according to the different affected brain regions (neural precursors, GABAergic interneurons, glu-tamatergic projection neurons, Bergmann glia). We also review human genetics data regarding the brain defects identified in patients carrying mutations within human SOX2 and examine the paral-lels with mouse mutants. Functional genomics approaches have started to identify SOX2 molecular targets, and their relevance for SOX2 function in brain development and disease will be discussed.

Mercurio, S., Serra, L., Pagin, M., Nicolis, S. (2022). Deconstructing Sox2 Function in Brain Development and Disease. CELLS, 11(10) [10.3390/cells11101604].

Deconstructing Sox2 Function in Brain Development and Disease

Mercurio S.
;
Serra L.;Pagin M.;Nicolis S. K.
2022

Abstract

SOX2 is a transcription factor conserved throughout vertebrate evolution, whose expression marks the central nervous system from the earliest developmental stages. In humans, SOX2 mutation leads to a spectrum of CNS defects, including vision and hippocampus impairments, in-tellectual disability, and motor control problems. Here, we review how conditional Sox2 knockout (cKO) in mouse with different Cre recombinases leads to very diverse phenotypes in different regions of the developing and postnatal brain. Surprisingly, despite the widespread expression of Sox2 in neural stem/progenitor cells of the developing neural tube, some regions (hippocampus, ventral forebrain) appear much more vulnerable than others to Sox2 deletion. Furthermore, the stage of Sox2 deletion is also a critical determinant of the resulting defects, pointing to a stage-specificity of SOX2 function. Finally, cKOs illuminate the importance of SOX2 function in different cell types according to the different affected brain regions (neural precursors, GABAergic interneurons, glu-tamatergic projection neurons, Bergmann glia). We also review human genetics data regarding the brain defects identified in patients carrying mutations within human SOX2 and examine the paral-lels with mouse mutants. Functional genomics approaches have started to identify SOX2 molecular targets, and their relevance for SOX2 function in brain development and disease will be discussed.
Articolo in rivista - Review Essay
brain; development; glia; neural stem cells; neurons; Sox2; transcription factor;
English
Mercurio, S., Serra, L., Pagin, M., Nicolis, S. (2022). Deconstructing Sox2 Function in Brain Development and Disease. CELLS, 11(10) [10.3390/cells11101604].
Mercurio, S; Serra, L; Pagin, M; Nicolis, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/384685
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