The transcription factor NFIA controls the onset of gliogenesis in the developing spinal cord.
The mechanisms controlling the transition from neurogenesis to gliogenesis in the vertebrate CNS are incompletely understood. We identified a family of transcription factors, called NFI genes, which are induced throughout the spinal cord ventricular zone (VZ) concomitantly with the induction of GLAST, an early marker of gliogenesis. NFIA is both necessary and sufficient for GLAST induction in the VZ. Unexpectedly, NFIA is also essential for the continued inhibition of neurogenesis in VZ progenitors. This function is mediated by the requirement of NFIA for the expression of HES5, a Notch effector. However, Notch effectors are unable to promote glial-fate specification in the absence of NFIA. Thus, NFIA links the abrogation of neurogenesis to a generic program of gliogenesis, in both astrocyte and oligodendrocyte VZ progenitors. At later stages, NFIA promotes migration and differentiation of astrocyte precursors, a function that is antagonized in oligodendrocyte precursors by Olig2.
Deneen
Benjamin
B
Division of Biology 216-76, California Institute of Technology, 1201 East California Boulevard, Pasadena, California 91125, USA.
Ho
Ritchie
R
Lukaszewicz
Agnes
A
Hochstim
Christian J
CJ
Gronostajski
Richard M
RM
Anderson
David J
DJ
D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002642:Chick Embryo; D004622:Embryo, Mammalian; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D051379:Mice; D046228:Microarray Analysis / Q000379:methods; D008954:Models, Biological; D051839:NFI Transcription Factors / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D000076104:Oligodendrocyte Transcription Factor 2; D038081:Organogenesis / Q000502:physiology*; D034622:RNA Interference / Q000502:physiology; D051880:Receptors, Notch / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000502:physiology; D013234:Stem Cells / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D027341:Excitatory Amino Acid Transporter 1; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D051839:NFI Transcription Factors; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D051880:Receptors, Notch; C497646:Nfia protein, mouse; C512773:Olig2 protein, mouse; C493393:Slc1a3 protein, mouse