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Researchers Identify Key Neuron Development Protein

September 6, 2009

Researchers at the University of Toronto have identified a protein which plays a key role in the development of neurons, which could enhance our understanding of how the brain works, and how diseases such as Alzheimer’s occur.

U of T graduate student John Calarco, working in the labs of Prof. Ben Blencowe (Donnelly Centre for Cellular and Biomolecular Research, University of Toronto) and Prof. Mei Zhen (Samuel Lunenfeld Research Institute, Mount Sinai Hospital), has identified a protein known as nSR100, which is only found in vertebrate species and which controls a network of “alternative splicing events” that are located in the messages of genes with critical functions in the formation of the nervous system. The findings are published in a paper in the current edition of the journal Cell.

Alternative splicing events greatly expand the diversity of the genetic messages and corresponding proteins produced by genes in vertebrate cells, and this process partially accounts for the evolution of remarkable complexity in organs such as the mammalian brain. Calarco, recipient of a prestigious Alexander Graham Bell Studentship, together with colleagues in the Blencowe Lab, identified nSR100 using computational and experimental methods and then determined its role in the control of alternative splicing in the brain. These studies revealed that nSR100 regulates splicing events in genes that help form neurons.

Collaborator and co-author Brian Ciruna and his colleagues at the Hospital for Sick Children (SickKids) in Torontofurther demonstrated that nSR100 plays a critical role in the development of the vertebrate nervous system.

“The brain is by far the most complex organ in the human body and understanding how it functions represents one of the foremost challenges of biomedical research. A large number of neurological disorders arise when the development and function of certain neurons is impaired. A major research goal is therefore to identify key genes required for the specification and function of neurons in the brain, and nSR100 represents such a gene,” said Prof. Blencowe, principal investigator on the study.

Calarco added that the findings present a new avenue of investigation for researchers. “The study provides intriguing insight into how the evolution of a single protein has contributed to the expansion of brain complexity in vertebrates ““ including humans.

Further investigation into the complex network of splicing events regulated by nSR100 may uncover important aspects of how neurons normally function and also how they become impaired in neurological diseases like Alzheimer’s.”

The authors’ research is supported by funds from the Canadian Institutes of Health Research, the Ontario Research Fund and Genome Canada through the Ontario Genomics Institute.

Cell Paper Authors:

John A. Calarco (Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, Department of Molecular Genetics, University of Toronto); Simone Superina (Department of Molecular Genetics, University of Toronto and Program in Developmental and Stem Cell Biology, The Hospital for Sick Children); Dave O’Hanlon (Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto); Mathieu Gabut (Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto);Bushra Raj (Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, Department of Molecular Genetics, University of Toronto); Qun Pan (Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto);Ursula Skalska (Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto); Laura Clarke(Department of Molecular Genetics, University of Toronto); Danielle Gelinas (Program in Developmental and Stem Cell Biology, The Hospital for Sick Children);Derek van der Kooy (Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, Department of Molecular Genetics, University of Toronto); Mei Zhen (Department of Molecular Genetics, University of Toronto and Samuel Lunenfeld Research Institute, Mount Sinai Hospital); Brian Ciruna (Department of Molecular Genetics, University of Toronto and Program in Developmental and Stem Cell Biology, The Hospital for Sick Children); Benjamin J. Blencowe (Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, Department of Molecular Genetics, University of Toronto and Centre for Bioinformatics, King’s College, University of London)

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