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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
Neuron | 2014

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.

Pubmed ID: 24814534

Research resources used in this publication

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Associated grants

  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG003988
  • Agency: PHS HHS, United States
    Id: T32 GMO7618
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007449
  • Agency: NINDS NIH HHS, United States
    Id: R01NS062859A
  • Agency: NIGMS NIH HHS, United States
    Id: F32 GM105202
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS099099
  • Agency: NHGRI NIH HHS, United States
    Id: R01HG003988
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS062859
  • Agency: NIMH NIH HHS, United States
    Id: R37 MH049428
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007618
  • Agency: NINDS NIH HHS, United States
    Id: R01NS34661
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH094589
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS034661

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Allen Developing Mouse Brain Atlas (tool)

RRID:SCR_002990

Map of gene expression in developing mouse brain revealing gene expression patterns from embryonic through postnatal stages. Provides information about spatial and temporal regulation of gene expression with database. Feature include seven sagittal reference atlases created with a developmental ontology. These anatomic atlases may be viewed alongside in situ hybridization (ISH) data as well as by itself.

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