| Popis: |
During neocortical development, neurons are produced by a diverse pool of neural progenitors. A subset of progenitors express theCux2gene 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 regulateCux2expression in the forebrain, we characterized a conservedCux2enhancer that we find recapitulatesCux2expression specifically in the cortical hem. Using a bioinformatic approach, we found several potential transcription factor (TF) binding sites for cortical hem-patterning TFs. We found that the homeobox transcription factor, Lmx1a, can activate theCux2enhancerin vitro. Furthermore, we show that multiple Lmx1a binding sites required for enhancer activity in the cortical hemin vivo. Mis-expression of Lmx1a in neocortical progenitors caused an increase inCux2+-lineage cells. Finally, we compared several conserved 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 regulatingCux2expression will increase our understanding of the mechanisms pivotal in establishingCux2-lineage fates in the developing forebrain.Summary StatementAnalysis of a cortical hem-specificCux2enhancer reveals role forLmx1aas a critical upstream regulator ofCux2expression patterns in neural progenitors during early forebrain development. |
