Format

Send to

Choose Destination
See comment in PubMed Commons below
Neuron. 2014 Jun 4;82(5):989-1003. doi: 10.1016/j.neuron.2014.04.014. Epub 2014 May 8.

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

Author information

1
Department of Psychiatry, Program in Neuroscience, Rock Hall, University of California at San Francisco, San Francisco, CA 94158-2324, USA.
2
Department of Psychiatry, Program in Neuroscience, Rock Hall, University of California at San Francisco, San Francisco, CA 94158-2324, USA; Acetylon Pharmaceuticals, Boston, MA 02210, USA.
3
Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
4
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA; Institute for Biostatistics and Informatics in Medicine and Ageing Research, Department of Medicine, University of Rostock, 18057 Rostock, Germany.
5
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
6
Allen Institute for Brain Science, Seattle, WA 98103, USA.
7
Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; U.S. Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA.
8
Department of Morphological Sciences, Faculty of Medicine, University of Murcia, E-30100 Murcia, Spain.
9
Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; U.S. Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA; School of Natural Sciences, University of California, Merced, Merced, CA 95343, USA.
10
Department of Psychiatry, Program in Neuroscience, Rock Hall, University of California at San Francisco, San Francisco, CA 94158-2324, USA. Electronic address: john.rubenstein@ucsf.edu.

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.

PMID:
24814534
PMCID:
PMC4104757
DOI:
10.1016/j.neuron.2014.04.014
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center