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Intermediate progenitors and Tbr2 in cortical development.

Robert F Hevner1

  • 1Department of Pathology, University of California, San Diego, CA, USA.

Journal of Anatomy
|January 25, 2019
PubMed
Summary
This summary is machine-generated.

The Tbr2 transcription factor is crucial for developing the cerebral cortex, guiding the production of projection neurons and regulating gene expression. Its absence leads to abnormal progenitor cells, highlighting its essential role in brain development.

Keywords:
EomesTbr2apoptosiscortex patterningcortical developmentintermediate progenitorsneurogenesis

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Intermediate progenitors (IPs) are key transit-amplifying cells in the developing cerebral cortex, derived from radial glia (RG) progenitors.
  • IPs exclusively generate glutamatergic projection neurons (PNs) and exist as distinct ventricular (vIP) and outer (oIP) subtypes.
  • IPs interact with RG cells via Delta-Notch signaling and secrete Cxcl12, influencing cell migration and axon growth.

Purpose of the Study:

  • To investigate the role of the T-box transcription factor Tbr2 (Eomes) in the development and function of intermediate progenitor cells (IPs) in the cerebral cortex.
  • To elucidate the molecular mechanisms by which Tbr2 regulates PN differentiation, subtype specification, and gene expression.
  • To understand the broader implications of Tbr2 function in cortical evolution and human brain development.

Main Methods:

  • Analysis of Tbr2 expression and function in developing mouse cerebral cortex.
  • Investigating the regulatory interactions between Tbr2, IP-genic transcription factors (e.g., Insm1, Pax6), and PN-specific genes (e.g., Tbr1).
  • Studying the epigenetic mechanisms involving Jmjd3 and polycomb repressive complex 2 in Tbr2-mediated gene activation.

Main Results:

  • Tbr2 is essential for PN differentiation and subtype specification, and it represses IP-genic transcription factors like Insm1 and Pax6.
  • Loss of Tbr2 function leads to transient accumulation of abnormal IPs.
  • Tbr2 regulates the transcriptome by activating or repressing hundreds of genes, including unlocking PN-specific genes like Tbr1 via epigenetic modifications.

Conclusions:

  • Tbr2 is a critical regulator of cortical development, essential for the precise generation of projection neurons.
  • Tbr2 controls progenitor cell fate and gene expression through direct transcriptional regulation and epigenetic modulation.
  • The function of Tbr2 is vital for the evolution of the mammalian cerebral cortex and is indispensable for human brain development.