SoxC Transcription Factors Are Required for Neuronal Differentiation in Adult Hippocampal Neurogenesis

Abstract

Neural stem cells (NSCs) generate new hippocampal dentate granule neurons throughout adulthood. The genetic programs controlling neuronal differentiation of adult NSCs are only poorly understood. Here we show that, in the adult mouse hippocampus, expression of the SoxC transcription factors Sox4 and Sox11 is initiated around the time of neuronal commitment of adult NSCs and is maintained in immature neurons. Overexpression of Sox4 and Sox11 strongly promotes in vitro neurogenesis from adult NSCs, whereas ablation of Sox4/Sox11 prevents in vitro and in vivo neurogenesis from adult NSCs. Moreover, we demonstrate that SoxC transcription factors target the promoters of genes that are induced on neuronal differentiation of adult NSCs. Finally, we show that reprogramming of astroglia into neurons is dependent on the presence of SoxC factors. These data identify SoxC proteins as essential contributors to the genetic network controlling neuronal differentiation in adult neurogenesis and neuronal reprogramming of somatic cells.

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

“…Table 3), indicating the more immature nature of reactive astrocytes compared with astrocytes in the intact brain. Notably, some neurogenic factors, such as Sox11 (sex‐determining region y‐box, 11) (Mu et al, 2012; Ninkovic et al 2013) are upregulated in reactive astrocytes, but do not reach the levels of the neurogenic priming observed in SEZ NSCs (Beckervordersandforth et al, 2010; Bracko et al, 2012; Götz et al, 2015). Consistent with some degree of cell fate change, the gliogenic genes, Nfib (nuclear factor I/B) and Sox9 are downregulated in reactive astrocytes compared with astrocytes from the intact brain.…”

Transcription Factors SOX4 and SOX11 Function Redundantly to Regulate the Development of Mouse Retinal Ganglion Cells

“…Overexpression of Sox4 or Sox11 in cultured retinal explants at E17 stimulates the differentiation of progenitor cells into cone cells at the cost of losing rod cells (23). Abrogation of Sox4/11 in vivo suppresses the differentiation of adult neuron stem cells and does not affect the apoptosis (20). In addition, knocking down of Sox4 is reported to damage proliferation of osteoblasts in vitro (37).…”

The early retinal progenitor-expressed gene Sox11 regulates the timing of the differentiation of retinal cells

“…Therefore, the altered differentiation is probably caused by the direct effects of Sox11 and Sox4 on retinal cell fate decision, rather than secondary effects resulting from perturbation of the timing of cell cycle exit. In adult mouse hippocampus, Sox4/Sox11 ablation decreased the generation of cells expressing neuron-specific proteins, without significant alterations in proliferation (Mu et al, 2012). However, evidence showing involvement of Sox11 in mantle cell lymphoma had been accumulated (Sander, 2011), and more recently, involvement of Sox4 in lung cancers was reported (Castillo et al, 2012), thus suggesting that Sox11 and Sox4 differently involve proliferation in CNS and other tissues.…”