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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

188 Scopus citations

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 languageAmerican English
Pages (from-to)895-908
Number of pages14
JournalCell
Volume152
Issue number4
DOIs
StatePublished - 14 Feb 2013

Bibliographical note

Funding Information:
The authors thank Julian Golder and Noah Efron for help with digital image acquisition and data processing; Bing Ren and Zirong Li for help with chromatin immunoprecipitation from embryonic mouse tissue; Inna Dubchak, Simon Minovitsky, and Alexandre Poliakov for website support; and staff at San Francisco General Hospital Women’s Options Center for their consideration in allowing us to access donated fetal tissue. A.V. and L.A.P. were supported by NINDS grant R01NS062859A and by NHGRI grant R01HG003988. J.L.R.R. was supported by the Nina Ireland, Weston Havens Foundation, NINDS grant R01NS34661, NIMH grant R01MH081880, and NIMH grant R37MH049428. J.L.R.R. and A.R.K. were supported by CIRM RB2-1602. G.M. and S.N.S. were supported by T32 GM007449, K.P. was supported by T32 GMO7618, R.H. was supported by F32 MH081431, and O.G. was supported by NARSAD. A.R.K. was supported by NINDS grant R01NS075998. I.O. was supported by the Intramural Research Program of the NIH, National Library of Medicine. Research was conducted at the E.O. Lawrence Berkeley National Laboratory and performed under Department of Energy Contract DE-AC02-05CH11231, University of California.

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