Differential modulation of BMP signaling promotes the elaboration of cerebral cortical GABAergic neurons or oligodendrocytes from a common sonic hedgehog-responsive ventral forebrain progenitor species

摘要: During cerebral cortical development, excitatory glutamatergic projection neurons are generated from neural stem cells intrinsic to the early embryonic ventricular zone by a process of radial migration, whereas most inhibitory γ-aminobutyric acid (GABA)ergic interneurons and oligodendrocytes (OLs) appear be elaborated ventral forebrain that initially undergo tangential migration before terminal lineage maturation. In contrast more compartmentalized developmental organization spinal cord, generation OLs common cell would expose these sequential actions dorsal gradient morphogens [sonic hedgehog (Shh) bone morphogenetic proteins (BMPs)] normally mediate opposing programs. Here we report Shh promotes GABAergic neuronal/OL restriction cells, in part, activation basic helix–loop–helix transcription factors, Olig2 Mash1. mutant mice with generalized defect (Dlx1/2−/−), there is profound selective reduction elaboration both OLs. Our studies further demonstrate Shh-responsive progenitors requires spatial temporal modulation BMP signaling ligands antagonist, noggin, respectively. These findings suggest an integrative model for neuronal OL maturation incorporate contributions forebrain, potential role regional cues modulating transcriptional codes within evolving species.