title: Transcriptional regulation of enhancers active in protodomains of the developing cerebral cortex.
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.
authors.affiliation: Department of Psychiatry, Program in Neuroscience, Rock Hall, University of California at San Francisco, San Francisco, CA 94158-2324, USA.
authors.forename: Kartik
authors.initials: K
authors.lastname: Pattabiraman
authors.affiliation: 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.
authors.forename: Olga
authors.initials: O
authors.lastname: Golonzhka
authors.affiliation: Department of Psychiatry, Program in Neuroscience, Rock Hall, University of California at San Francisco, San Francisco, CA 94158-2324, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Lindtner
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Alex S
authors.initials: AS
authors.lastname: Nord
authors.affiliation: 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.
authors.forename: Leila
authors.initials: L
authors.lastname: Taher
authors.affiliation: Department of Psychiatry, Program in Neuroscience, Rock Hall, University of California at San Francisco, San Francisco, CA 94158-2324, USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Hoch
authors.affiliation: Department of Psychiatry, Program in Neuroscience, Rock Hall, University of California at San Francisco, San Francisco, CA 94158-2324, USA.
authors.forename: Shanni N
authors.initials: SN
authors.lastname: Silberberg
authors.affiliation: Department of Psychiatry, Program in Neuroscience, Rock Hall, University of California at San Francisco, San Francisco, CA 94158-2324, USA.
authors.forename: Dongji
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98103, USA.
authors.forename: HongKui
authors.initials: H
authors.lastname: Zeng
authors.affiliation: 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.
authors.forename: Len A
authors.initials: LA
authors.lastname: Pennacchio
authors.affiliation: Department of Morphological Sciences, Faculty of Medicine, University of Murcia, E-30100 Murcia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Puelles
authors.affiliation: 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.
authors.forename: Axel
authors.initials: A
authors.lastname: Visel
authors.affiliation: 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.
authors.forename: John L R
authors.initials: JL
authors.lastname: Rubenstein
mesh_terms: D000818:Animals; D001665:Binding Sites; D051838:COUP Transcription Factor I / Q000378:metabolism; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005136:Eye Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D051838:COUP Transcription Factor I; D005136:Eye Proteins; D018398:Homeodomain Proteins; C497590:Nr2f1 protein, mouse; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C481797:Pbx1 protein, mouse; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D012097:Repressor Proteins; D014157:Transcription Factors