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Tissue-Specific Actions of Pax6 on the Balance of Proliferation and Differentiation in Developing Forebrain are Foxg1-Dependent

72 Pages Posted: 7 Jan 2019 Sneak Peek Status: Published

See all articles by Idoia Quintana‐Urzainqui

Idoia Quintana‐Urzainqui

Simons Initiative for the Developing Brain

Zrinko Kozić

Simons Initiative for the Developing Brain

Soham Mitra

Simons Initiative for the Developing Brain

Tian Tian

Simons Initiative for the Developing Brain

Martine Manuel

Simons Initiative for the Developing Brain

John O. Mason

Simons Initiative for the Developing Brain

David J. Price

Simons Initiative for the Developing Brain

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Abstract

Differences in the growth and maturation of diverse forebrain tissues depend on region-specific transcriptional regulation. Individual transcription factors act simultaneously in multiple regions that develop very differently, raising questions about the extent to which their actions vary regionally. We found that the transcription factor Pax6 affects the transcriptomes and the balance between proliferation and differentiation in opposite directions in diencephalon versus cerebral cortex. We tested several possible mechanisms to explain Pax6’s tissue-specific actions and found that the presence of the transcription factor Foxg1 in cortex but not diencephalon was most influential. We found that Foxg1 is responsible for many of the differences in cell cycle gene expression between diencephalon and cortex and, in cortex lacking Foxg1, Pax6’s action on the balance of proliferation versus differentiation becomes diencephalon-like. Our findings reveal a mechanism for generating regional forebrain diversity in which one transcription factor completely reverses the actions of another.

Suggested Citation

Quintana‐Urzainqui, Idoia and Kozić, Zrinko and Mitra, Soham and Tian, Tian and Manuel, Martine and Mason, John O. and Price, David J., Tissue-Specific Actions of Pax6 on the Balance of Proliferation and Differentiation in Developing Forebrain are Foxg1-Dependent (September 14, 2018). Available at SSRN: https://ssrn.com/abstract=3249469 or http://dx.doi.org/10.2139/ssrn.3249469
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Idoia Quintana‐Urzainqui (Contact Author)

Simons Initiative for the Developing Brain

Hugh Robson Building
George Square
Edinburgh, EH8 9XD
United Kingdom

Zrinko Kozić

Simons Initiative for the Developing Brain

Hugh Robson Building
George Square
Edinburgh, EH8 9XD
United Kingdom

Soham Mitra

Simons Initiative for the Developing Brain

Hugh Robson Building
George Square
Edinburgh, EH8 9XD
United Kingdom

Tian Tian

Simons Initiative for the Developing Brain

Hugh Robson Building
George Square
Edinburgh, EH8 9XD
United Kingdom

Martine Manuel

Simons Initiative for the Developing Brain

Hugh Robson Building
George Square
Edinburgh, EH8 9XD
United Kingdom

John O. Mason

Simons Initiative for the Developing Brain

Hugh Robson Building
George Square
Edinburgh, EH8 9XD
United Kingdom

David J. Price

Simons Initiative for the Developing Brain

Hugh Robson Building
George Square
Edinburgh, EH8 9XD
United Kingdom

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