title: Neurog2 is a direct downstream target of the Ptf1a-Rbpj transcription complex in dorsal spinal cord.
abstract: PTF1-J is a trimeric transcription factor complex essential for generating the correct balance of GABAergic and glutamatergic interneurons in multiple regions of the nervous system, including the dorsal horn of the spinal cord and the cerebellum. Although the components of PTF1-J have been identified as the basic helix-loop-helix (bHLH) factor Ptf1a, its heterodimeric E-protein partner, and Rbpj, no neural targets are known for this transcription factor complex. Here we identify the neuronal differentiation gene Neurog2 (Ngn2, Math4A, neurogenin 2) as a direct target of PTF1-J. A Neurog2 dorsal neural tube enhancer localized 3' of the Neurog2 coding sequence was identified that requires a PTF1-J binding site for dorsal activity in mouse and chick neural tube. Gain and loss of Ptf1a function in vivo demonstrate its role in Neurog2 enhancer activity. Furthermore, chromatin immunoprecipitation from neural tube tissue demonstrates that Ptf1a is bound to the Neurog2 enhancer. Thus, Neurog2 expression is directly regulated by the PTF1-J complex, identifying Neurog2 as the first neural target of Ptf1a and revealing a bHLH transcription factor cascade functioning in the specification of GABAergic neurons in the dorsal spinal cord and cerebellum.
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: R Michael
authors.initials: RM
authors.lastname: Henke
authors.forename: Trisha K
authors.initials: TK
authors.lastname: Savage
authors.forename: David M
authors.initials: DM
authors.lastname: Meredith
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Glasgow
authors.forename: Kei
authors.initials: K
authors.lastname: Hori
authors.forename: Judy
authors.initials: J
authors.lastname: Dumas
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: MacDonald
authors.forename: Jane E
authors.initials: JE
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002454:Cell Differentiation / Q000502:physiology; D002642:Chick Embryo; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C102938:Neurog2 protein, mouse; C497571:Rbpj protein, mouse; C062602:transcription factor PTF1