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Molecule awakens and maintains neural connections

Researchers have discovered a critical protein that regulates the growth and activation of neural connections in the brain. The protein functions in the developing brain, where it controls the sprouting of new connections and stimulates otherwise silent connections among immature neurons, and potentially in the mature brain as well, where it may play a role in memory formation.

The researchers published their discovery of the protein, called dendrite arborization and synapse maturation 1, or Dasm1, in two papers in the September 7, 2004, issue of the Proceedings of the National Academy of Sciences. They were led by Howard Hughes Medical Institute investigators Yuh Nung Jan and Lily Yeh Jan. The first author on both papers was Song-Hai Shi in the Jans' laboratory at the University of California, San Francisco.

Dendritic spines are mushroom-shaped protuberances that extend from the surface of the cable-like axon of a neuron. Dendrites receive chemical signals that trigger nerve impulses in the form of neurotransmitters launched from neighboring neurons. Growth of new dendrites can therefore increase the connection between neurons. Changes in the strength of connections, known as long-term potentiation, allow the brain to create memories.

In exploring the growth and development of dendritic spines, Shi, the Jans, and their colleagues first identified a gene in the fruit fly Drosophila that appears to play a role in regulating dendrite growth, or "arborization." In comparing the fruit fly gene with databases of vertebrate genomes, they identified a similar homologue in mice, which they named Dasm1.

Their initial studies revealed that the gene was highly expressed in the brains of embryonic mice. "A major reason we became interested in this molecule is that when we used antibody markers to look at the distribution of the protein, we saw it primarily in the dendrites, with very little in the axons," said Yuh Nung Jan. "If you look
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
13-Sep-2004


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