Open AccessLmx1a drives Cux2 expression in the cortical hem through activation of a conserved intronic enhancer
Author(s) -
Santiago P. Fregoso,
Brett E. Dwyer,
Santos J. Franco
Publication year - 2019
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.170068
Subject(s) - biology , enhancer , genetics , microbiology and biotechnology , expression (computer science) , conserved sequence , transcription factor , gene , evolutionary biology , base sequence , computer science , programming language
During neocortical development, neurons are produced by a diverse pool of neural progenitors. A subset of progenitors express the Cux2 gene and are fate-restricted to produce certain neuronal subtypes, but the upstream pathways that specify these progenitor fates remain unknown. To uncover the transcriptional networks that regulate Cux2 expression in the forebrain, we characterized a conserved Cux2 enhancer that recapitulates Cux2 expression specifically in the cortical hem. Using a bioinformatic approach, we identified putative transcription factor (TF) binding sites for cortical hem-patterning TFs. We found that the homeobox TF, Lmx1a, can activate the Cux2 enhancer in vitro. Furthermore, we showed that Lmx1a binding sites were required for enhancer activity in the cortical hem in vivo. Mis-expression of Lmx1a in hippocampal progenitors caused an increase in Cux2 enhancer activity outside the cortical hem. Finally, we compared several human enhancers with cortical hem-restricted activity and found that recurrent Lmx1a binding sites are a top shared feature. Uncovering the network of TFs involved in regulating Cux2 expression will increase our understanding of the mechanisms pivotal in establishing Cux2-lineage fates in the developing forebrain.