Neurog2 is a direct downstream target of the Ptf1a-Rbpj transcription complex in dorsal spinal cord
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 identifie...
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Published in | Development (Cambridge) Vol. 136; no. 17; pp. 2945 - 2954 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
The Company of Biologists Limited
01.09.2009
Company of Biologists |
Subjects | |
Online Access | Get full text |
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Summary: | 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 3â² 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 We thank Dr Robert Hammer and the outstanding service of the UT Southwestern Transgenic Core Facility for generating the transgenic mice for this study. We acknowledge Drs G. Swift, K. Zimmerman, H. Lai and E. J. Kim for critical comments on the manuscript. This work was supported by NIH Public Health Service grants R01-HD37932 (J.E.J.), R01-DK61220 (R.J.M.) and T32-MH076690 (D.M.M.). Deposited in PMC for release after 12 months. These authors contributed equally to this work Author for correspondence (jane.johnson@utsouthwestern.edu) |
ISSN: | 0950-1991 1477-9129 |
DOI: | 10.1242/dev.035352 |