title: Oligodendrocyte development in the embryonic tuberal hypothalamus and the influence of Ascl1.
abstract: Although the vast majority of cells in our brains are glia, we are only beginning to understand programs governing their development, especially within the embryonic hypothalamus. In mice, gliogenesis is a protracted process that begins during embryonic stages and continues into the early postnatal period, with glial progenitors first producing oligodendrocyte precursor cells, which then differentiate into pro-oligodendrocytes, pro-myelinating oligodendrocytes, and finally, mature myelinating oligodendrocytes. The exact timing of the transition from neurogenesis to gliogenesis and the subsequent differentiation of glial lineages remains unknown for most of the Central Nervous System (CNS), and is especially true for the hypothalamus.
  
  
  
  Here we used mouse embryonic brain samples to determine the onset of gliogenesis and expansion of glial populations in the tuberal hypothalamus using glial markers Sox9, Sox10, Olig2, PdgfRα, Aldh1L1, and MBP. We further employed Ascl1 and Neurog2 mutant mice to probe the influence of these proneual genes on developing embryonic gliogenic populations.
  
  
  
  Using marker analyses for glial precursors, we found that gliogenesis commences just prior to E13.5 in the tuberal hypothalamus, beginning with the detection of glioblast and oligodendrocyte precursor cell markers in a restricted domain adjacent to the third ventricle. Sox9+ and Olig2+ glioblasts are also observed in the mantle region from E13.5 onwards, many of which are Ki67+ proliferating cells, and peaks at E17.5. Using Ascl1 and Neurog2 mutant mice to investigate the influence of these bHLH transcription factors on the progression of gliogenesis in the tuberal hypothalamus, we found that the elimination of Ascl1 resulted in an increase in oligodendrocyte cells throughout the expansive period of oligodendrogenesis.
  
  
  
  Our results are the first to define the timing of gliogenesis in the tuberal hypothalamus and indicate that Ascl1 is required to repress oligodendrocyte differentiation within this brain region.
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Department of Pharmacology & Physiology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
authors.forename: Candace M
authors.initials: CM
authors.lastname: Marsters
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Rosin
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
authors.forename: Hayley F
authors.initials: HF
authors.lastname: Thornton
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
authors.forename: Shaghayegh
authors.initials: S
authors.lastname: Aslanpour
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Klenin
authors.affiliation: Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
authors.forename: Grey
authors.initials: G
authors.lastname: Wilkinson
authors.affiliation: Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Biological Sciences Platform, Sunnybrook Research Institute, Toronto, ON, M4N 3M5, Canada.
authors.forename: Carol
authors.initials: C
authors.lastname: Schuurmans
authors.affiliation: Department of Pharmacology & Physiology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.
authors.forename: Quentin J
authors.initials: QJ
authors.lastname: Pittman
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada. kurrasch@ucalgary.ca.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada. kurrasch@ucalgary.ca.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Kurrasch
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D007026:Hypothalamic Area, Lateral / Q000196:embryology*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D058953:Neural Stem Cells / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C499317:Ascl1 protein, mouse; C102938:Neurog2 protein, mouse
keywords: Ascl1; Astrocyte; Gliogenesis; Neurog2; Olig2; Oligodendrogenesis; PdgfRα; Sox9