TY - JOUR
T1 - Transcriptional regulation of enhancers active in protodomains of the developing cerebral cortex
AU - Pattabiraman, Kartik
AU - Golonzhka, Olga
AU - Lindtner, Susan
AU - Nord, Alex S
AU - Taher, Leila
AU - Hoch, Renee
AU - Silberberg, Shanni N
AU - Zhang, Dongji
AU - Chen, Bin
AU - Zeng, HongKui
AU - Pennacchio, Len A
AU - Puelles, Luis
AU - Visel, Axel
AU - Rubenstein, John L R
N1 - Copyright © 2014 Elsevier Inc. All rights reserved.
PY - 2014/6/4
Y1 - 2014/6/4
N2 - 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.
AB - 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.
KW - Animals
KW - Binding Sites
KW - COUP Transcription Factor I/metabolism
KW - Cerebral Cortex/embryology
KW - Enhancer Elements, Genetic
KW - Eye Proteins/metabolism
KW - Gene Expression Regulation, Developmental
KW - Hippocampus/embryology
KW - Homeodomain Proteins/metabolism
KW - Humans
KW - Mice
KW - Mice, Transgenic
KW - PAX6 Transcription Factor
KW - Paired Box Transcription Factors/metabolism
KW - Pre-B-Cell Leukemia Transcription Factor 1
KW - Repressor Proteins/metabolism
KW - Transcription Factors/metabolism
KW - Transcription, Genetic
U2 - 10.1016/j.neuron.2014.04.014
DO - 10.1016/j.neuron.2014.04.014
M3 - Article
C2 - 24814534
SN - 0896-6273
VL - 82
SP - 989
EP - 1003
JO - Neuron
JF - Neuron
IS - 5
ER -