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Transcriptional network orchestrating regional patterning of cortical progenitors.

Athéna R YpsilantiKartik PattabiramanRinaldo Catta-PretaOlga GolonzhkaSusan LindtnerKe TangIan R JonesArmen AbnousiIvan JuricMing HuYin ShenDiane E DickelAxel ViselLen A PennachioMichael HawrylyczCarol L ThompsonHongkui ZengIros BarozziAlexander S NordJohn L R Rubenstein
Published in: Proceedings of the National Academy of Sciences of the United States of America (2022)
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.
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