1. Transcriptional network orchestrating regional patterning of cortical progenitors
- Author
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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, Pennachio, Len A, Hawrylycz, Michael, Thompson, Carol L, Zeng, Hongkui, Barozzi, Iros, Nord, Alex S, and Rubenstein, John L
- Subjects
Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Biological Sciences ,Stem Cell Research - Nonembryonic - Non-Human ,Genetics ,Human Genome ,Stem Cell Research ,1.1 Normal biological development and functioning ,Neurological ,Animals ,COUP Transcription Factor I ,Cerebral Cortex ,Epigenome ,Gene Regulatory Networks ,Homeodomain Proteins ,LIM-Homeodomain Proteins ,Mice ,PAX6 Transcription Factor ,Pre-B-Cell Leukemia Transcription Factor 1 ,Regulatory Elements ,Transcriptional ,Transcription Factors ,cortical patterning ,epigenetics ,transcription factors ,progenitor cells - 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.
- Published
- 2021