Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons
Abstract
The embryonic basal ganglia generates multiple projection neurons and interneuron subtypes from distinct progenitor domains. Combinatorial interactions of transcription factors and chromatin are thought to regulate gene expression. In the medial ganglionic eminence, the NKX2-1 transcription factor controls regional identity and, with LHX6, is necessary to specify pallidal projection neurons and forebrain interneurons. Here, we dissected the molecular functions of NKX2-1 by defining its chromosomal binding, regulation of gene expression, and epigenetic state. NKX2-1 binding at distal regulatory elements led to a repressed epigenetic state and transcriptional repression in the ventricular zone. Conversely, NKX2-1 is required to establish a permissive chromatin state and transcriptional activation in the sub-ventricular and mantle zones. Moreover, combinatorial binding of NKX2-1 and LHX6 promotes transcriptionally permissive chromatin and activates genes expressed in cortical migrating interneurons. Our integrated approach gives a foundation for elucidating transcriptional networks guiding the development of the MGE and its descendants.
- Authors:
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1393685
- Alternate Identifier(s):
- OSTI ID: 1393077
- Grant/Contract Number:
- AC02- 05CH11231; AC02-05CH11231
- Resource Type:
- Published Article
- Journal Name:
- Neuron
- Additional Journal Information:
- Journal Name: Neuron Journal Volume: 91 Journal Issue: 6; Journal ID: ISSN 0896-6273
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Sandberg, Magnus, Flandin, Pierre, Silberberg, Shanni, Su-Feher, Linda, Price, James D., Hu, Jia Sheng, Kim, Carol, Visel, Axel, Nord, Alex S., and Rubenstein, John L. R. Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons. United States: N. p., 2016.
Web. doi:10.1016/j.neuron.2016.08.020.
Sandberg, Magnus, Flandin, Pierre, Silberberg, Shanni, Su-Feher, Linda, Price, James D., Hu, Jia Sheng, Kim, Carol, Visel, Axel, Nord, Alex S., & Rubenstein, John L. R. Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons. United States. https://doi.org/10.1016/j.neuron.2016.08.020
Sandberg, Magnus, Flandin, Pierre, Silberberg, Shanni, Su-Feher, Linda, Price, James D., Hu, Jia Sheng, Kim, Carol, Visel, Axel, Nord, Alex S., and Rubenstein, John L. R. Thu .
"Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons". United States. https://doi.org/10.1016/j.neuron.2016.08.020.
@article{osti_1393685,
title = {Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons},
author = {Sandberg, Magnus and Flandin, Pierre and Silberberg, Shanni and Su-Feher, Linda and Price, James D. and Hu, Jia Sheng and Kim, Carol and Visel, Axel and Nord, Alex S. and Rubenstein, John L. R.},
abstractNote = {The embryonic basal ganglia generates multiple projection neurons and interneuron subtypes from distinct progenitor domains. Combinatorial interactions of transcription factors and chromatin are thought to regulate gene expression. In the medial ganglionic eminence, the NKX2-1 transcription factor controls regional identity and, with LHX6, is necessary to specify pallidal projection neurons and forebrain interneurons. Here, we dissected the molecular functions of NKX2-1 by defining its chromosomal binding, regulation of gene expression, and epigenetic state. NKX2-1 binding at distal regulatory elements led to a repressed epigenetic state and transcriptional repression in the ventricular zone. Conversely, NKX2-1 is required to establish a permissive chromatin state and transcriptional activation in the sub-ventricular and mantle zones. Moreover, combinatorial binding of NKX2-1 and LHX6 promotes transcriptionally permissive chromatin and activates genes expressed in cortical migrating interneurons. Our integrated approach gives a foundation for elucidating transcriptional networks guiding the development of the MGE and its descendants.},
doi = {10.1016/j.neuron.2016.08.020},
journal = {Neuron},
number = 6,
volume = 91,
place = {United States},
year = {Thu Sep 01 00:00:00 EDT 2016},
month = {Thu Sep 01 00:00:00 EDT 2016}
}
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https://doi.org/10.1016/j.neuron.2016.08.020
https://doi.org/10.1016/j.neuron.2016.08.020
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