title: The homeobox gene Gsx2 controls the timing of oligodendroglial fate specification in mouse lateral ganglionic eminence progenitors.
abstract: The homeobox gene Gsx2 has previously been shown to be required for the specification of distinct neuronal subtypes derived from lateral ganglionic eminence (LGE) progenitors at specific embryonic time points. However, its role in the subsequent generation of oligodendrocytes from these progenitors remains unclear. We have utilized conditional gain-of-function and loss-of-function approaches in order to elucidate the role of Gsx2 in the switch between neurogenesis and oligodendrogenesis within the embryonic ventral telencephalon. In the absence of Gsx2 expression, an increase in oligodendrocyte precursor cells (OPCs) with a concomitant decrease in neurogenesis is observed in the subventricular zone of the LGE at mid-stages of embryogenesis (i.e. E12.5-15.5), which subsequently leads to an increased number of Gsx2-derived OPCs within the adjacent mantle regions of the cortex before birth at E18.5. Moreover, using Olig2(cre) to conditionally inactivate Gsx2 throughout the ventral telencephalon with the exception of the dorsal (d)LGE, we found that the increase in cortical OPCs in Gsx2 germline mutants are derived from dLGE progenitors. We also show that Ascl1 is required for the expansion of these dLGE-derived OPCs in the cortex of Gsx2 mutants. Complementing these results, gain-of-function experiments in which Gsx2 was expressed throughout most of the late-stage embryonic telencephalon (i.e. E15.5-18.5) result in a significant decrease in the number of cortical OPCs. These results support the notion that high levels of Gsx2 suppress OPC specification in dLGE progenitors and that its downregulation is required for the transition from neurogenesis to oligodendrogenesis.
authors: Divisions of Developmental Biology and Neurosurgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors: Heather
authors: H
authors: Chapman
authors: Ronald R
authors: RR
authors: Waclaw
authors: Zhenglei
authors: Z
authors: Pei
authors: Masato
authors: M
authors: Nakafuku
authors: Kenneth
authors: K
authors: Campbell
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D019070:Cell Lineage; D005724:Ganglia / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000502:physiology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology; D013687:Telencephalon / Q000502:physiology; D013997:Time Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D020796:Receptor, Platelet-Derived Growth Factor alpha; D055757:SOXE Transcription Factors; C109498:Gsh2 protein, mouse; C512773:Olig2 protein, mouse; C527924:Sox10 protein, mouse
keywords: Cell-fate specification; Mouse; Olig2; Oligodendrocyte precursor cell; Pdgfrα; Sox10; Telencephalon
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