A High-Resolution Enhancer Atlas of the Developing Telencephalon.

Publication Year: 
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 Kaplan
Arnold R Kriegstein
Edward M Rubin
Ivan Ovcharenko
Len A Pennacchio
John L R Rubenstein
PubMed link: 
Public Summary: 
This paper describes the first large scale identification of parts of the human chromosome that control gene expression in parts of the embryonic brain. This information can be used to facilitate basic research on stem cells that generate neurons, and to help identify causes of human disorders of brain development.
Scientific 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.