Anterior CNS expansion driven by brain transcription factors

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Abstract

During CNS development there is prominent expansion of the anterior region, the brain. In Drosophila, anterior CNS expansion emerges from three rostral features: 1) increased progenitor cell generation, 2) extended progenitor cell proliferation, 3) more proliferative daughters. We find that tailless (mouse Nr2E1/Tlx), otp/Rx/hbn (Otp/Arx/Rax) and Doc1/2/3 (Tbx2/3/6) are important for brain progenitor generation. These genes, and earmuff (FezF1/2), are also important for subsequent progenitor and/or daughter cell proliferation in the brain. Brain TF co-misexpression can drive brain-profile proliferation in the nerve cord, and can reprogram developing wing discs into brain neural progenitors. Brain TF expression is promoted by the PRC2 complex, acting to keep the brain free of anti-proliferative and repressive action of Hox homeotic genes. Hence, anterior expansion of the Drosophila CNS is mediated by brain TF driven 'super-generation' of progenitors, as well as 'hyper-proliferation' of progenitor and daughter cells, promoted by PRC2-mediated repression of Hox activity.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Jesús Rodriguez Curt

Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden

Competing interests
The authors declare that no competing interests exist.
Behzad Yaghmaeian Salmani

Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden

Competing interests
The authors declare that no competing interests exist.
Stefan Thor

Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden

For correspondence
stefan.thor@liu.se

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5095-541X

Funding

Knut och Alice Wallenbergs Stiftelse (KAW2011.0165)

Stefan Thor

Vetenskapsrådet (621-2013-5258)

Stefan Thor

Cancerfonden (140780; 150663)

Stefan Thor

Knut och Alice Wallenbergs Stiftelse (KAW2012.0101)

Stefan Thor

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.