title: The protomap is propagated to cortical plate neurons through an Eomes-dependent intermediate map.
abstract: 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.
authors: Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA.
authors: Gina E
authors: GE
authors: Elsen
authors: Rebecca D
authors: RD
authors: Hodge
authors: Francesco
authors: F
authors: Bedogni
authors: Ray A M
authors: RA
authors: Daza
authors: Branden R
authors: BR
authors: Nelson
authors: Naoko
authors: N
authors: Shiba
authors: Steven L
authors: SL
authors: Reiner
authors: Robert F
authors: RF
authors: Hevner
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019521:Body Patterning; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000033:anatomy & histology* / Q000254:growth & development / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C491198:Eomes protein, mouse; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; C492271:Tbr1 protein, mouse