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CTCF is a key molecule involved in generating Neuronal Diversity and in formation of Functional Neural Networks -- a world first!

2012-7-27(Fri)

Under the leadership of Specially Appointed Assistant Professor Teruyoshi HIRAYAMA and Professor Takeshi YAGI of the Graduate School of Frontier Biosciences, Osaka University, a group of researchers have --for the first time in the world-- clarified a key regulator in a molecular mechanism for generating diversity in individual neurons and the relation of this mechanism to the development of dendrites in the formation of functional neural networks in the cerebral cortex.

The research by the group showed that CCCTC-binding protein was a factor in change in the chromatin architecture in the nucleus of each cell and this protein controlled the expression of clustered protocadherin (Pcdh) genes in each neuron. Additionally, a lack of CTCF protein caused abnormality in neural networks, indicating that CTCF regulates neural diversity and formation of neural networks. The group examined expression regulation of (Pcdh) genes in individual neurons in mice with CTCF-deficient neurons and found Pcdh gene expression was significantly decreased in each neuron .

This research achievement has clarified that CTCF is a regulatory agent for Pcdh expression and that CTCF  is essential for forming functional chromatin architecture and neural networks. These results show that change in chromatin architecture in each neuron is essential for forming functional neural networks, a foundation of brain function. These findings will greatly assist in the elucidation of human neuropsychiatric disorders and the development of new therapeutic methods.

This research was conducted in cooperation with Assistant Professor Etsuko TARUSAWA, Professor Yumiko YOSHIMURA of the National Institute for Physiological Sciences, and Dr. Niels Galjart of the Erasmus Medical Center, The Netherlands.

 

Note: This thesis made the cover of Volume 2, Issue 2, of Cell Reports. (August 31, 2012)

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To read the full research report entitled "ICTCF Is Required for Neural Development and Stochastic Expression of Clustered Pcdh Genes in Neurons," please go to this page at the Cell Reports website.


Related links:

KOKORO Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University

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