The protomap is propagated to cortical plate neurons through an Eomes -dependent intermediate map
Copyright policy )The protomap is propagated to cortical plate neurons through an Eomes -dependent intermediate map
The cortical area map is initially patterned by transcription factor (TF) gradients in the neocortical primordium, which define a “protomap” in the embryonic ventricular zone (VZ). However, mechanisms that propagate regional identity from VZ progenitors to cortical plate (CP) neurons are unknown. Here we show that the VZ, subventricular zone (SVZ), and CP contain distinct molecular maps of regional identity, reflecting different gene expression gradients in radial glia progenitors, intermediate progenitors, and projection neurons, respectively. The “intermediate map” in the SVZ is modulated by Eomes (also known as Tbr2), a T-box TF. Eomes inactivation caused rostrocaudal shifts in SVZ and CP gene expression, with loss of corticospinal axons and gain of corticotectal projections. These findings suggest that cortical areas and connections are shaped by sequential maps of regional identity, propagated by the Pax6 → Eomes → Tbr1 TF cascade. In humans, PAX6 , EOMES , and TBR1 have been linked to intellectual disability and autism.
- King’s University United States
- University of Mary United States
- University of Washington United States
- Columbia University United States
- Seattle Children's Research Institute United States
Cerebral Cortex, Homeodomain Proteins, Mice, Knockout, Neurons, Brain Mapping, PAX6 Transcription Factor, Gene Expression, Mice, Transgenic, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Intellectual Disability, Neural Pathways, Animals, Humans, Paired Box Transcription Factors, Female, Autistic Disorder, Eye Proteins, Body Patterning
Cerebral Cortex, Homeodomain Proteins, Mice, Knockout, Neurons, Brain Mapping, PAX6 Transcription Factor, Gene Expression, Mice, Transgenic, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Intellectual Disability, Neural Pathways, Animals, Humans, Paired Box Transcription Factors, Female, Autistic Disorder, Eye Proteins, Body Patterning
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