Wnts Influence the Timing and Efficiency of Oligodendrocyte Precursor Cell Generation in the Telencephalon

Abstract

Oligodendrocyte precursor cells (OPCs) are generated from multiple progenitor domains in the telencephalon in developmental succession from ventral to dorsal. Previous studies showed that Wnt signaling inhibits the differentiation of OPCs into mature oligodendrocytes. Here we explored the hypothesis that Wnt signaling limits the generation of OPCs from neural progenitors during forebrain development. We manipulated Wnt signaling in mouse neural progenitor cultures and found that Wnt signaling influences progenitors cell autonomously to alter the production of OPCs, and that endogenous Wnt signaling in these cultures limits the efficiency of generating OPCs from neural progenitors. To examine these eventsin vivo, we electroporated a soluble Wnt inhibitor or a dominant-negative transcriptional regulator into embryonic mouse neocortical ventricular zone before the usual onset of OPC production and showed that decreasing Wnt signaling in cortical progenitors results in early production of OPCs. Our studies indicate that Wnt signaling influences the timing and extent of OPC production in the developing telencephalon.

β-Catenin signaling specifies progenitor cell identity in parallel with Shh signaling in the developing mammalian thalamus

“…4F). Although Wnt/-catenin signaling inhibits the formation of oligodendrocyte precursor cells (Zhong et al, 2011;Ye et al, 2009;Langseth et al, 2010), we did not find an increase in cells expressing Pdgfr, a marker for oligodendrocyte precursor cells (supplementary material Fig. S12E,F).…”

Oligodendrocyte Development and Plasticity

“…In keeping with this interpretation, SVZ stem cells express high levels of the Egf receptor (Egfr, ErbB1), whereas OPCs do not (Chojnacki and Weiss 2004;Sun et al 2005;Cahoy et al 2008), and Egf has been reported not to stimulate proliferation of OPCs or other neural cells outside of the SVZ in slice culture (Hill et al 2013). (Canoll et al 1996;Vartanian et al 1999;Fernandez et al 2000;Carteron et al 2006;Brinkmann et al 2008;Taveggia et al 2008;Ortega et al 2012), Wnts (Shimizu et al 2005;Fancy et al 2009;Ye et al 2009;Langseth et al 2010;Dai et al 2014), neurotrophin-3 Cohen et al 1996), chemokines (Robinson et al 1998;Dziembowska et al 2005;Göttle et al 2010), ciliary neuronotrophic factor ), brain-derived neurotrophic factor (Vondran et al 2010;Wong et al 2013), transferrin (Silvestroff et al 2013), erythropoetin (Sugawa et al 2002), thyroid hormone (TH; triiodothyronine) (Walters and Morell 1981;Barres et al 1994;Ahlgren et al 1997;Rodriguez-Pena 1999), retinoic acid (Barres et al 1994;Noll and Miller 1994), and others. Most of these factors influence the differentiation of OLs and/or their subsequent survival including, perhaps especially, during demyelination and remyelination.…”

Wnt/Rspondin/β-catenin signals control axonal sorting and lineage progression in Schwann cell development

“…Mice with floxed β-catenin alleles to produce LOF and GOF mutants and Rosa STOP -YFP fl , Cnp-cre, and Axin2-LacZ mice were previously described (30,33,34,50,51).…”