Transcriptional network orchestrating regional patterning of cortical progenitors

Athena R. Ypsilanti, Kartik Pattabiraman, Rinaldo Catta-Preta, Olga Golonzhka, Susan Lindtner, Ke Tang, Ian R. Jones, Armen Abnousi, Ivan Juric, Ming Hu, Yin Shen, Diane E. Dickel, Axel Visel, Len A. Pennacchio, Michael Hawrylycz, Carol L. Thompson, Hongkui Zeng, Iros Barozzi, Alex S. Nord, John L. Rubenstein

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article numbere2024795118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number51
DOIs
StatePublished - Dec 21 2021

Keywords

  • Cortical patterning
  • Epigenetics
  • Progenitor cells
  • Transcription factors

ASJC Scopus subject areas

  • General

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