Neurog2 is a direct downstream target of the Ptf1a-Rbpj transcription complex in dorsal spinal cord

R. Michael Henke, Trisha K. Savage, David M. Meredith, Stavey M. Glasgow, Kei Hori, Judy Dumas, Raymond J. MacDonald, Jane E. Johnson

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2945-2954
Number of pages10
JournalDevelopment
Volume136
Issue number17
DOIs
StatePublished - Sep 1 2009

Fingerprint

Neural Tube
Spinal Cord
Cerebellum
Transcription Factors
Basic Helix-Loop-Helix Transcription Factors
GABAergic Neurons
Chromatin Immunoprecipitation
Interneurons
Nervous System
Binding Sites
Genes
Proteins

Keywords

  • bHLH transcription factor
  • Cerebellum development
  • Dorsal neural tube development
  • Gene regulation
  • Mouse
  • Spinal cord development

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Henke, R. M., Savage, T. K., Meredith, D. M., Glasgow, S. M., Hori, K., Dumas, J., ... Johnson, J. E. (2009). Neurog2 is a direct downstream target of the Ptf1a-Rbpj transcription complex in dorsal spinal cord. Development, 136(17), 2945-2954. https://doi.org/10.1242/dev.035352

Neurog2 is a direct downstream target of the Ptf1a-Rbpj transcription complex in dorsal spinal cord. / Henke, R. Michael; Savage, Trisha K.; Meredith, David M.; Glasgow, Stavey M.; Hori, Kei; Dumas, Judy; MacDonald, Raymond J.; Johnson, Jane E.

In: Development, Vol. 136, No. 17, 01.09.2009, p. 2945-2954.

Research output: Contribution to journalArticle

Henke RM, Savage TK, Meredith DM, Glasgow SM, Hori K, Dumas J et al. Neurog2 is a direct downstream target of the Ptf1a-Rbpj transcription complex in dorsal spinal cord. Development. 2009 Sep 1;136(17):2945-2954. https://doi.org/10.1242/dev.035352
Henke, R. Michael ; Savage, Trisha K. ; Meredith, David M. ; Glasgow, Stavey M. ; Hori, Kei ; Dumas, Judy ; MacDonald, Raymond J. ; Johnson, Jane E. / Neurog2 is a direct downstream target of the Ptf1a-Rbpj transcription complex in dorsal spinal cord. In: Development. 2009 ; Vol. 136, No. 17. pp. 2945-2954.
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