Transcriptional regulation of enhancers active in protodomains of the developing cerebral cortex

Kartik Pattabiraman, Olga Golonzhka, Susan Lindtner, Alex S Nord, Leila Taher, Renee Hoch, Shanni N Silberberg, Dongji Zhang, Bin Chen, HongKui Zeng, Len A Pennacchio, Luis Puelles, Axel Visel, John L R Rubenstein

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Elucidating the genetic control of cerebral cortical (pallial) development is essential for understanding function, evolution, and disorders of the brain. Transcription factors (TFs) that embryonically regulate pallial regionalization are expressed in gradients, raising the question of how discrete domains are generated. We provide evidence that small enhancer elements active in protodomains integrate broad transcriptional information. CreER(T2) and GFP expression from 14 different enhancer elements in stable transgenic mice allowed us to define a comprehensive regional fate map of the pallium. We explored transcriptional mechanisms that control the activity of the enhancers using informatics, in vivo occupancy by TFs that regulate cortical patterning (CoupTFI, Pax6, and Pbx1), and analysis of enhancer activity in Pax6 mutants. Overall, the results provide insights into how broadly expressed patterning TFs regulate the activity of small enhancer elements that drive gene expression in pallial protodomains that fate map to distinct cortical regions.

Original languageEnglish
Pages (from-to)989-1003
Number of pages15
JournalNeuron
Volume82
Issue number5
DOIs
Publication statusPublished - 4 Jun 2014

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Keywords

  • Animals
  • Binding Sites
  • COUP Transcription Factor I/metabolism
  • Cerebral Cortex/embryology
  • Enhancer Elements, Genetic
  • Eye Proteins/metabolism
  • Gene Expression Regulation, Developmental
  • Hippocampus/embryology
  • Homeodomain Proteins/metabolism
  • Humans
  • Mice
  • Mice, Transgenic
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors/metabolism
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Repressor Proteins/metabolism
  • Transcription Factors/metabolism
  • Transcription, Genetic

Cite this

Pattabiraman, K., Golonzhka, O., Lindtner, S., Nord, A. S., Taher, L., Hoch, R., ... Rubenstein, J. L. R. (2014). Transcriptional regulation of enhancers active in protodomains of the developing cerebral cortex. Neuron, 82(5), 989-1003. https://doi.org/10.1016/j.neuron.2014.04.014