The protomap is propagated to cortical plate neurons through an Eomes -dependent intermediate map
Open accessAbstract
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.
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Differential gene expression and gradients of signaling molecules across the embryonic brain generate prospective subdivisions of the neocortex.
“More specifically, it is well documented that differential gene expression and the gradients of signaling molecules across the embryonic brain generate prospective subdivisions of the neocortex [24–29].”
From Development of prefrontal cortex (2022) · cites this paper as [26]
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“However, it remains to be seen as to whether the transcriptional regulation in these regions is similar to that studied in the SVZ (Sessa et al. 2008; Cameron et al. 2012; Elsen et al. 2013).”
BackgroundMethodResultInfluentialEvolution and development of the mammalian cerebral cortex
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- Authors
- Elsen, G. E., Hodge, R. D., Bedogni, F., Daza, R. A. M., Nelson, B. R., Shiba, N., Reiner, S. L., & Hevner, R. F.
- Affiliations
- Seattle Children's Research Institute (US)
- University of Washington (US)
- Columbia University (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-02-19
- Volume
- 110
- Issue
- 10
- Pages
- 4081-4086
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3593833
- OpenAlex
- W2171983806
- Cited by
- 87
- References
- 47
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 9 · 2022: 4 · 2021: 8 · 2020: 6 · 2019: 10 · 2018: 6 · 2017: 3 · 2016: 9 · 2015: 6 · 2014: 9 · 2013: 7
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI061699)
- National Institute of Neurological Disorders and Stroke (R01NS050248, NS050248)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- Eomes, Tbr2, T-box transcription factor, Pax6, Tbr1, ventricular zone, subventricular zone, intermediate progenitor cells, corticospinal axons, corticotectal projections, intellectual disability, autism spectrum disorder
- MeSH terms
- PAX6 Transcription Factor, Animals, Autistic Disorder, Brain Mapping, Cerebral Cortex, DNA-Binding Proteins, Eye Proteins, Female, Humans, Intellectual Disability, Mice, Inbred C57BL, Mice, Transgenic, Neural Pathways, Neurons, Pregnancy, Repressor Proteins, Signal Transduction, Gene Expression, Mice, Knockout, Homeodomain Proteins, Body Patterning, T-Box Domain Proteins, Mice, Paired Box Transcription Factors
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