Identification of a transient Sox5 expressing progenitor population in the neonatal ventral forebrain by a novel cis-regulatory element

Abstract

Precise control of lineage-specific gene expression in the neural stem/progenitor cells is crucial for generation of the diversity of neuronal and glial cell types in the central nervous system (CNS). The mechanism underlying such gene regulation, however, is not fully elucidated. Here, we report that a 377 bp evolutionarily conserved DNA fragment (CR5), located approximately 32 kbp upstream of Olig2 transcription start site, acts as a cis-regulator for gene expression in the development of the neonatal forebrain. CR5 is active in a time-specific and brain region-restricted manner. CR5 activity is not detected in the embryonic stage, but it is exclusively in a subset of Sox5+ cells in the neonatal ventral forebrain. Furthermore, we show that Sox5 binding motif in CR5 is important for this cell-specific gene regulatory activity; mutation of Sox5 binding motif in CR5 alters reporter gene expression with different cellular composition. Together, our study provides new insights into the regulation of cell-specific gene expression during CNS development.

Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice

“…The SOX5 gene belongs to a family of SOXD transcription factors (sex‐determining region‐related HMG‐box) and is involved in multiple developmental processes including nervous system development. SOX5 mediates postmitotic differentiation of early progenitor neurons, regulates neuron migration, postmigratory differentiation, axonal projection development and development of cortical layer‐dependent corticofugal projections . Crucial role of SOX5 in neurodevelopment and corticogenesis is confirmed in both mice and drosophila models .…”

“…projections. [42][43][44] Crucial role of SOX5 in neurodevelopment and corticogenesis is confirmed in both mice and drosophila models. 43,45 SCN3A have been mostly associated with CNV, 46 Table S1) and Jhaveri et al 50 had polymicrogyria.…”

Identification of Hypoxia-Specific Biomarkers in Salmonids Using RNA-Sequencing and Validation Using High-Throughput qPCR

“…Consistent with the suppression of genes involved in cell proliferation, theexpression of genes involved in blocking the cell cycle progression i.e., transcription factor SOX-5 (SOX-5), CDKN1B, and malignant fibrous histiocytoma-amplified sequence 1 homolog (MFHAS1) were among the top 10 hypoxia-induced upregulated genes discovered in this study. Sox-5 is well known for its function in controlling cell cycle and sequential generation of distinct corticofugal neuron subtypes (Hao et al 2014). The upregulation of SOX-5 occurs in response to hypoxia in human stem cells (Khan et al 2007).…”

SOX5/6/21 Prevent Oncogene-Driven Transformation of Brain Stem Cells

“…The HMG-box SOX transcription factor family members SOX5, SOX6, and SOX21 (SOX5/6/21) are widely expressed in NSCs of the CNS (7)(8)(9)(10)(11)(12) and when overexpressed can promote embryonic NSCs to exit the cell cycle and commit to differentiation (13,14). Interestingly, a common feature of these SOX transcription factors is their capability to counteract tumor cell expansion, as in vitro experiments have shown that forced expression of SOX5 and SOX21 decreases the viability of human glioma cell lines (15,16).…”