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Title: Transcriptional network orchestrating regional patterning of cortical progenitors

Abstract

We uncovered a transcription factor (TF) network that regulates cortical regional patterning in radial glial stem cells. Screening the expression of hundreds of TFs in the developing mouse cortex identified 38 TFs that are expressed in gradients in the ventricular zone (VZ). We tested whether their cortical expression was altered in mutant mice with known patterning defects (Emx2, Nr2f1, and Pax6), which enabled us to define a cortical regionalization TF network (CRTFN). To identify genomic programming underlying this network, we performed TF ChIP-seq and chromatin-looping conformation to identify enhancer–gene interactions. To map enhancers involved in regional patterning of cortical progenitors, we performed assays for epigenomic marks and DNA accessibility in VZ cells purified from wild-type and patterning mutant mice. This integrated approach has identified a CRTFN and VZ enhancers involved in cortical regional patterning in the mouse.

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [2];  [1];  [1]; ORCiD logo [3];  [1];  [4];  [4]; ORCiD logo [4];  [1];  [5];  [6];  [7];  [8]; ORCiD logo [8]; ORCiD logo [8]; ORCiD logo [9]; ORCiD logo [2]; ORCiD logo [1]
  1. Univ. of California, San Francisco, CA (United States)
  2. Univ. of California, Davis, CA (United States)
  3. Guangzhou Univ. (China)
  4. Cleveland Clinic Foundation, Cleveland, OH (United States)
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  6. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); ; Univ. of California, Merced, CA (United States); USDOE Joint Genome Institute (JGI), Berkeley, CA (United States)
  7. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); ; Univ. of California, Berkeley, CA (United States); USDOE Joint Genome Institute (JGI), Berkeley, CA (United States)
  8. Allen Institute for Brain Science, Seattle, WA (United States)
  9. Imperial College, London (United Kingdom)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE; National Institute of Neurological Disorders and Stroke; National Institute of Mental Health; National Institute of General Medical Sciences; National Institutes of Health (NIH); Imperial College Research Fellowship; National Institute of Health; National Cancer Institute (NCI)
OSTI Identifier:
1860335
Alternate Identifier(s):
OSTI ID: 1907579
Grant/Contract Number:  
AC02-05CH11231; R01NS34661; R01 MH049428; R35 GM119831; U54DK107977; P30CA082103; R01HG003988; R01HG00398
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 118; Journal Issue: 51; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; cortical patterning; epigenetics; transcription factors; progenitor cells; Cortical regional patterning; Emx2; Nr2f1; Pax6; enhancers; transcription; chromatin conformation

Citation Formats

Ypsilanti, Athéna R., Pattabiraman, Kartik, Catta-Preta, Rinaldo, Golonzhka, Olga, Lindtner, Susan, Tang, Ke, Jones, Ian R., Abnousi, Armen, Juric, Ivan, Hu, Ming, Shen, Yin, Dickel, Diane E., Visel, Axel, Pennacchio, Len A., Hawrylycz, Michael, Thompson, Carol L., Zeng, Hongkui, Barozzi, Iros, Nord, Alex S., and Rubenstein, John L. Transcriptional network orchestrating regional patterning of cortical progenitors. United States: N. p., 2021. Web. doi:10.1073/pnas.2024795118.
Ypsilanti, Athéna R., Pattabiraman, Kartik, Catta-Preta, Rinaldo, Golonzhka, Olga, Lindtner, Susan, Tang, Ke, Jones, Ian R., Abnousi, Armen, Juric, Ivan, Hu, Ming, Shen, Yin, Dickel, Diane E., Visel, Axel, Pennacchio, Len A., Hawrylycz, Michael, Thompson, Carol L., Zeng, Hongkui, Barozzi, Iros, Nord, Alex S., & Rubenstein, John L. Transcriptional network orchestrating regional patterning of cortical progenitors. United States. https://doi.org/10.1073/pnas.2024795118
Ypsilanti, Athéna R., Pattabiraman, Kartik, Catta-Preta, Rinaldo, Golonzhka, Olga, Lindtner, Susan, Tang, Ke, Jones, Ian R., Abnousi, Armen, Juric, Ivan, Hu, Ming, Shen, Yin, Dickel, Diane E., Visel, Axel, Pennacchio, Len A., Hawrylycz, Michael, Thompson, Carol L., Zeng, Hongkui, Barozzi, Iros, Nord, Alex S., and Rubenstein, John L. Fri . "Transcriptional network orchestrating regional patterning of cortical progenitors". United States. https://doi.org/10.1073/pnas.2024795118. https://www.osti.gov/servlets/purl/1860335.
@article{osti_1860335,
title = {Transcriptional network orchestrating regional patterning of cortical progenitors},
author = {Ypsilanti, Athéna R. and Pattabiraman, Kartik and Catta-Preta, Rinaldo and Golonzhka, Olga and Lindtner, Susan and Tang, Ke and Jones, Ian R. and Abnousi, Armen and Juric, Ivan and Hu, Ming and Shen, Yin and Dickel, Diane E. and Visel, Axel and Pennacchio, Len A. and Hawrylycz, Michael and Thompson, Carol L. and Zeng, Hongkui and Barozzi, Iros and Nord, Alex S. and Rubenstein, John L.},
abstractNote = {We uncovered a transcription factor (TF) network that regulates cortical regional patterning in radial glial stem cells. Screening the expression of hundreds of TFs in the developing mouse cortex identified 38 TFs that are expressed in gradients in the ventricular zone (VZ). We tested whether their cortical expression was altered in mutant mice with known patterning defects (Emx2, Nr2f1, and Pax6), which enabled us to define a cortical regionalization TF network (CRTFN). To identify genomic programming underlying this network, we performed TF ChIP-seq and chromatin-looping conformation to identify enhancer–gene interactions. To map enhancers involved in regional patterning of cortical progenitors, we performed assays for epigenomic marks and DNA accessibility in VZ cells purified from wild-type and patterning mutant mice. This integrated approach has identified a CRTFN and VZ enhancers involved in cortical regional patterning in the mouse.},
doi = {10.1073/pnas.2024795118},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 51,
volume = 118,
place = {United States},
year = {Fri Dec 17 00:00:00 EST 2021},
month = {Fri Dec 17 00:00:00 EST 2021}
}

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