A high-resolution enhancer atlas of the developing telencephalon

Axel Visel, Leila Taher, Hani Girgis, Dalit May, Olga Golonzhka, Renee V Hoch, Gabriel L McKinsey, Kartik Pattabiraman, Shanni N Silberberg, Matthew J Blow, David V Hansen, Alex S Nord, Jennifer A Akiyama, Amy Holt, Roya Hosseini, Sengthavy Phouanenavong, Ingrid Plajzer-Frick, Malak Shoukry, Veena Afzal, Tommy KaplanArnold R Kriegstein, Edward M Rubin, Ivan Ovcharenko, Len A Pennacchio, John L R Rubenstein

Research output: Contribution to journalArticlepeer-review

Abstract

The mammalian telencephalon plays critical roles in cognition, motor function, and emotion. Though many of the genes required for its development have been identified, the distant-acting regulatory sequences orchestrating their in vivo expression are mostly unknown. Here, we describe a digital atlas of in vivo enhancers active in subregions of the developing telencephalon. We identified more than 4,600 candidate embryonic forebrain enhancers and studied the in vivo activity of 329 of these sequences in transgenic mouse embryos. We generated serial sets of histological brain sections for 145 reproducible forebrain enhancers, resulting in a publicly accessible web-based data collection comprising more than 32,000 sections. We also used epigenomic analysis of human and mouse cortex tissue to directly compare the genome-wide enhancer architecture in these species. These data provide a primary resource for investigating gene regulatory mechanisms of telencephalon development and enable studies of the role of distant-acting enhancers in neurodevelopmental disorders.

Original languageEnglish
Pages (from-to)895-908
Number of pages14
JournalCell
Volume152
Issue number4
DOIs
Publication statusPublished - 14 Feb 2013

Keywords

  • Animals
  • Embryo, Mammalian/metabolism
  • Enhancer Elements, Genetic
  • Fetus/metabolism
  • Genome-Wide Association Study
  • Humans
  • Mice
  • Telencephalon/embryology
  • Transcriptome
  • p300-CBP Transcription Factors/metabolism

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