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  A network of genetic repression and derepression specifies projection fates in the developing neocortex

Srinivasan, K., Leone, D. P., Bateson, R. K., Dobreva, G., Kohwi, Y., Kohwi-Shigematsu, T., et al. (2012). A network of genetic repression and derepression specifies projection fates in the developing neocortex. Proceedings of the National Academy of Sciences of the United States of America, 109, 19071-19078. doi:10.1073/pnas.1216793109.

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https://www.pnas.org/content/109/47/19071 (Publisher version)
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 Creators:
Srinivasan, Karpagam1, Author
Leone, Dino P.1, Author
Bateson, Rosalie K.1, Author
Dobreva, Gergana2, Author              
Kohwi, Yoshinori1, Author
Kohwi-Shigematsu, Terumi1, Author
Grosschedl, Rudolf2, Author              
McConnell, Susan K.1, Author
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1External Organizations, ou_persistent22              
2Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              

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Free keywords: cell fate; cerebral cortex; axon guidance; transcription factor
 Abstract: Neurons within each layer in the mammalian cortex have stereotypic projections. Four genes-Fezf2, Ctip2, Tbr1, and Satb2-regulate these projection identities. These genes also interact with each other, and it is unclear how these interactions shape the final projection identity. Here we show, by generating double mutants of Fezf2, Ctip2, and Satb2, that cortical neurons deploy a complex genetic switch that uses mutual repression to produce subcortical or callosal projections. We discovered that Tbr1, EphA4, and Unc5H3 are critical downstream targets of Satb2 in callosal fate specification. This represents a unique role for Tbr1, implicated previously in specifying corticothalamic projections. We further show that Tbr1 expression is dually regulated by Satb2 and Ctip2 in layers 2-5. Finally, we show that Satb2 and Fezf2 regulate two disease-related genes, Auts2 (Autistic Susceptibility Gene2) and Bhlhb5 (mutated in Hereditary Spastic Paraplegia), providing a molecular handle to investigate circuit disorders in neurodevelopmental diseases.

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Language(s): eng - English
 Dates: 2012-11-20
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1073/pnas.1216793109
 Degree: -

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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : PNAS
  Other : Proceedings of the National Academy of Sciences of the USA
  Abbreviation : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
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Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 109 Sequence Number: - Start / End Page: 19071 - 19078 Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230