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Volume 17, Number 19, Issue of October 1, 1997 pp. 7425-7432
Copyright ©1997 Society for NeuroscienceThe Swiss Cheese Mutant Causes Glial Hyperwrapping and Brain Degeneration in Drosophila
Received March 3, 1997; revised July 8, 1997; accepted July 11, 1997.
Doris Kretzschmar1, 2, Gaiti Hasan3, Sugandha Sharma3, Martin Heisenberg4, and Seymour Benzer2 1 Lehrstuhl für Entwicklungsbiologie, Universität Regensburg, 93040 Regensburg, Germany, 2 Division of Biology, California Institute of Technology, Pasadena, California 91125, 3 National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560012, India, and 4 Lehrstuhl für Genetik, Theodor-Boveri Institut für Biowissenschaften, 97074 Würzburg, Germany
Swiss cheese (sws) mutant flies develop normally during larval life but show age-dependent neurodegeneration in the pupa and adult and have reduced life span. In late pupae, glial processes form abnormal, multilayered wrappings around neurons and axons. Degeneration first becomes evident in young flies as apoptosis in single scattered cells in the CNS, but later it becomes severe and widespread. In the adult, the number of glial wrappings increases with age. The sws gene is expressed in neurons in the brain cortex. The conceptual 1425 amino acid protein shows two domains with homology to the regulatory subunits of protein kinase A and to conceptual proteins of yet unknown function in yeast, worm, and human. Sequencing of two sws alleles shows amino acid substitutions in these two conserved domains. It is suggested that the novel SWS protein plays a role in a signaling mechanism between neurons and glia that regulates glial wrapping during development of the adult brain.
Key words: Drosophila; adult central nervous system; apoptosis; glia-neuron interaction; neurodegeneration; reduced life span
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