title: Mutual antagonism between Sox10 and NFIA regulates diversification of glial lineages and glioma subtypes.
abstract: Lineage progression and diversification is regulated by the coordinated action of unique sets of transcription factors. Oligodendrocytes (OL) and astrocytes (AS) comprise the glial sub-lineages in the CNS, and the manner in which their associated regulatory factors orchestrate lineage diversification during development and disease remains an open question. Sox10 and NFIA are key transcriptional regulators of gliogenesis associated with OL and AS. We found that NFIA inhibited Sox10 induction of OL differentiation through direct association and antagonism of its function. Conversely, we found that Sox10 antagonized NFIA function and suppressed AS differentiation in mouse and chick systems. Using this developmental paradigm as a model for glioma, we found that this relationship similarly regulated the generation of glioma subtypes. Our results describe the antagonistic relationship between Sox10 and NFIA that regulates the balance of OL and AS fate during development and demonstrate for the first time, to the best of our knowledge, that the transcriptional processes governing glial sub-lineage diversification oversee the generation of glioma subtypes.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Glasgow
authors.affiliation: 1] Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA. [2] Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: C Claus
authors.initials: CC
authors.lastname: Stolt
authors.affiliation: 1] Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA. [2] Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Teng-Wei
authors.initials: TW
authors.lastname: Huang
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, USA.
authors.forename: Fuyi
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: LoTurco
authors.affiliation: 1] Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA. [2] Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas, USA. [3] Department of Pediatrics, Neurology, and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA. [4] Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jeffrey L
authors.identifier: 0000000256285872
authors.initials: JL
authors.lastname: Neul
authors.affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Wegner
authors.affiliation: Department of Pathology, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Mohila
authors.affiliation: 1] Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA. [2] Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, Texas, USA. [3] Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA. [4] Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas, USA. [5] Department of Pediatrics, Neurology, and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA. [6] Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Deneen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002642:Chick Embryo; D047369:Chromatin Immunoprecipitation; D018274:Electroporation; D004622:Embryo, Mammalian; D005910:Glioma / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D000076104:Oligodendrocyte Transcription Factor 2; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D004676:Myelin Basic Protein; D051839:NFI Transcription Factors; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D055757:SOXE Transcription Factors; C497646:Nfia protein, mouse; C491328:Nkx6-1 protein, mouse; C512773:Olig2 protein, mouse; C527923:SOX10 protein, human