Distal-less genesDlx1/Dlx2repress oligodendrocyte genesis through transcriptional inhibition ofOlig2expression in the developing vertebrate forebrain

Abstract

Figures: 7 References: 48 Jiang et al DLX1/2 represses Olig2 expression in developing forebrain 2 Distal-less genes Dlx1/Dlx2 repress oligodendrocyte genesis through transcriptional inhibition of Olig2 expression in the developing vertebrate forebrain ABSTRACTIn this study, we demonstrate that mouse DLX2 binds to the Olig2 gene locus in mouse embryonic forebrain in vivo. We further confirm the specificity and the transcriptional repressive effect of the binding in vitro. Furthermore, loss of Dlx1/2 function leads to increased Olig2 expression in the ventral embryonic mouse forebrain in vivo. As well, we demonstrate that chicken DLX1 binds to one chicken Olig2 gene domain in vitro, and overexpression of Dlx1 is sufficient to repress Olig2 expression in the developing chicken forebrain in ovo. Chicken DLX1 with a mutation eliminating its DNA binding ability is unable to bind to the Olig2 probe in vitro, and abrogates its repressive function on Olig2 expression in ovo. Our results establish that Dlx1/2 is both necessary and sufficient to repress oligodendrocyte specification mediated via direct transcriptional inhibition of Olig2 expression in the developing vertebrate forebrain.

Genetic Regulation of Vertebrate Forebrain Development by Homeobox Genes

“…Additionally, DLX proteins promote the differentiation of GABAergic and cholinergic interneuron subtypes through regulation of Lhx6 and Lhx8 , where both Lhx genes have reduced expression in Dlx1/2 double homozygous mutants ( Petryniak et al, 2007 ; Long et al, 2009 ). DLX2 also downregulates Olig2 expression to repress oligodendrocyte development in early neurogenesis, and hence may control the balance between oligodendrocyte and neuron production ( Petryniak et al, 2007 ; Jiang et al, 2020 ). ASCL1, in turn, represses Dlx2 expression in later developmental stages, to allow the expression of Olig2 and promote oligodendrocyte production ( Petryniak et al, 2007 ; Poitras et al, 2007 ).…”

miR-17∼92 exerts stage-specific effects in adult V-SVZ neural stem cell lineages

“…However, the V-SVZ also generates oligodendrocytes destined for the corpus callosum, via OLIG2 + TACs (Menn et al, 2006;Nait-Oumesmar et al, 1999;Ortega et al, 2013). Importantly, over-expression and knock-out of Dlx2 or Olig2 is sufficient to shift progenitor cells into a neurogenic or oligodendrogenic fate respectively (Boshans et al, 2021;Jiang et al, 2020;Petryniak et al, 2007). Given the enrichment of miR-17$92 targets in 'oligodendrogenesis', we focused on whether cluster deletion results in a shift towards oligodendrogenesis in the adult V-SVZ.…”

miR-17∼92 exerts stage-specific effects in adult V-SVZ neural stem cell lineages

“…However, the V-SVZ also gives rise to oligodendrocytes, via OLIG2 + TACs (Menn et al, 2006). Importantly, over-expression and knock-out of Dlx2 or Olig2 is sufficient to shift progenitor cells into a neurogenic or oligodendrogenic fate respectively (Boshans et al, 2021;Jiang et al, 2020;Petryniak et al, 2007).…”