title: Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord.
abstract: Glia constitute the majority of cells in the mammalian central nervous system and are crucial for neurological function. However, there is an incomplete understanding of the molecular control of glial cell development. We find that the transcription factor Ascl1 (Mash1), which is best known for its role in neurogenesis, also functions in both astrocyte and oligodendrocyte lineages arising in the mouse spinal cord at late embryonic stages. Clonal fate mapping in vivo reveals heterogeneity in Ascl1-expressing glial progenitors and shows that Ascl1 defines cells that are restricted to either gray matter (GM) or white matter (WM) as astrocytes or oligodendrocytes. Conditional deletion of Ascl1 post-neurogenesis shows that Ascl1 is required during oligodendrogenesis for generating the correct numbers of WM but not GM oligodendrocyte precursor cells, whereas during astrocytogenesis Ascl1 functions in balancing the number of dorsal GM protoplasmic astrocytes with dorsal WM fibrous astrocytes. Thus, in addition to its function in neurogenesis, Ascl1 marks glial progenitors and controls the number and distribution of astrocytes and oligodendrocytes in the GM and WM of the spinal cord.
authors.affiliation: Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Tou Yia
authors.initials: TY
authors.lastname: Vue
authors.affiliation: Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Euiseok J
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Division of Molecular Neurobiology, MRC National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Parras
authors.affiliation: Division of Molecular Neurobiology, MRC National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Francois
authors.initials: F
authors.lastname: Guillemot
authors.affiliation: Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA jane.johnson@utsouthwestern.edu.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D051379:Mice; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C499317:Ascl1 protein, mouse
keywords: Astrocyte heterogeneity; Glial specification; Oligodendrogenesis; Spinal cord gliogenesis