The protomap is propagated to cortical plate neurons through an Eomes-dependent intermediate map

Gina E. Elsen, Rebecca D. Hodge, Francesco Bedogni, Ray A M Daza, Branden R. Nelson, Naoko Shiba, Steven L. Reiner, Robert F. Hevner

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4081-4086
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number10
DOIs
Publication statusPublished - Mar 5 2013

Keywords

  • Arealization
  • Bcl6
  • Bhlhb5
  • Patterning

ASJC Scopus subject areas

  • General

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    Elsen, G. E., Hodge, R. D., Bedogni, F., Daza, R. A. M., Nelson, B. R., Shiba, N., Reiner, S. L., & Hevner, R. F. (2013). The protomap is propagated to cortical plate neurons through an Eomes-dependent intermediate map. Proceedings of the National Academy of Sciences of the United States of America, 110(10), 4081-4086. https://doi.org/10.1073/pnas.1209076110