Sox2 is required for olfactory pit formation and olfactory neurogenesis through BMP restriction and Hes5 upregulation

Abstract

The transcription factor Sox2 is necessary to maintain pluripotency of embryonic stem cells, and to regulate neural development. Neurogenesis in the vertebrate olfactory epithelium persists from embryonic stages through adulthood. The role Sox2 plays for the development of the olfactory epithelium and neurogenesis within has, however, not been determined. Here, by analysing Sox2 conditional knockout mouse embryos and chick embryos deprived of Sox2 in the olfactory epithelium using CRISPR-Cas9, we show that Sox2 activity is crucial for the induction of the neural progenitor gene Hes5 and for subsequent differentiation of the neuronal lineage. Our results also suggest that Sox2 activity promotes the neurogenic domain in the nasal epithelium by restricting Bmp4 expression. The Sox2-deficient olfactory epithelium displays diminished cell cycle progression and proliferation, a dramatic increase in apoptosis and finally olfactory pit atrophy. Moreover, chromatin immunoprecipitation data show that Sox2 directly binds to the Hes5 promoter in both the PNS and CNS. Taken together, our results indicate that Sox2 is essential to establish, maintain and expand the neuronal progenitor pool by suppressing Bmp4 and upregulating Hes5 expression.

Molecular network of miR-1343 regulates the pluripotency of porcine pluripotent stem cells via repressing OTX2 expression

“…Our observation proved the concept similar to the previous reported result that Otx2 prevented the accumulation of neural progenitors [41]. Although Sox2 is the key pluripotent transcription factor to stabilize ESCs in a pluripotent state by maintaining the expression level of Oct4 [42,43], it also is an important factor regulating neurogenesis and is essential for neuronal progenitor formation and maintenance [44]. In human embryonic neural precursor cells, Sox2 is reported to repress Otx2 expression, whereas the ChIP-qPCR shows that Otx2 is able to target the promoter region of Sox2 and reduce Sox2 expression [27].…”

Codingde novomutations identified by WGS reveal novel orofacial cleft genes

“…To confirm a plausible role in orofacial morphogenesis and cleft pathogenesis, expression patterns of these genes were probed in the embryonic tissues forming the upper lip and primary palate in the mouse. As demonstrated previously, Sox2 expression was localized to the nasal pit epithelium at the center of the lambdoidal junction 30 . All candidate genes examined were detected in the neural crest mesenchyme, with several exhibiting expression adjacent to the Sox2 domain in the nasal pit, including Zfhx4, Mac1, and Setd2.…”

Genetic liability for internalizing versus externalizing behavior manifests in the developing and adult hippocampus: Insight from a meta-analysis of transcriptional profiling studies in a selectively-bred rat model

“…Many of our top differentially-expressed genes were also important regulators of cell fate. In addition to Bmp4, Sox9, Sox2, Hes Family BHLH Transcription Factor 5 (Hes5), Cd24, and Tek regulate functions such as the developmental progression of neural differentiation, gliogenesis, and endothelial proliferation (72, 80, 81, 83, 111–113). Differential expression of genes within these pathways is clearly relevant to neurodevelopmental programming ( discussed above ), but many of these genes were differentially expressed in adulthood – indeed, some of the effects appeared more robust.…”