Project description:Excitatory projection neurons of the neocortex can be classified as occupying the upper layers, layers 2-4, or the deep layers, layers 5 and 6. It is still unclear which transcription factors are required to specify one cell fate versus another and which downstream targets confer specific aspects of neuronal identity over developmental time. To identify transcription factors that specify upper layer versus deep layer fate, we analyzed cell type specific gene expression and differential chromatin accessibility over three defined stages of development. We found that transcription factor expression can distinguish upper layers from deep layers, and cell type specific transcription factor genes have differentially accessible chromatin in their regulatory domains, which tends to be correlated with gene expression.
Project description:Excitatory projection neurons of the neocortex can be classified as occupying the upper layers, layers 2-4, or the deep layers, layers 5 and 6. It is still unclear which transcription factors are required to specify one cell fate versus another and which downstream targets confer specific aspects of neuronal identity over developmental time. To identify transcription factors that specific upper layer versus deep layer fate, we analyzed cell type specific gene expression and differential chromatin accessibility over three defined stages of development. We found that transcription factor expression can distinguish upper layers from deep layers, and cell type-specific transcription factor genes have differentially accessible chromatin in their regulatory domains, which tends to be correlated with gene expression.
Project description:We recently published genetic lineage-tracing experiments using the Fezf2 and Cux2 loci. These experiments demonstrated that at both the clonal and population levels Fezf2(+) RGCs are multipotent and that at the population level Cux2(+) RGCs are multipotent. Here, we extend our work on the lineages of Fezf2(+) and Cux2(+) RGCs. Clonal analysis of E10.5 neocortical progenitors suggests that most, if not all, Cux2(+) and Fezf2(+) RGCs generate diverse projection neuron subtypes located throughout layers 2-6. These results support our previous conclusion that both Fezf2(+) and Cux2(+) RGCs are multipotent neocortical progenitors. This Matters Arising Response paper addresses the Gil-Sanz et al. (2015) Matters Arising paper, published concurrently in Neuron.
Project description:Gene expression of subtypes of neocortical projection neurons over developmental time is correlated with cell class-specific chromatin accessibility