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MBC in Press, published online ahead of print January 9, 2002
Mol. Biol. Cell 10.1091/mbc.01-07-0362

A more recent version of this article appeared on February 1, 2002
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Submitted on July 24, 2001
Revised on October 18, 2001
Accepted on November 1, 2001

Drosophila Stathmin: A Microtubule Destabilizing Factor Involved in Nervous System Formation

Sylvie Ozon1, Anton Guichet2, Olivier Gavet3, Siegfried Roth2, and André Sobel4*

1 FRE 2371 CNRS-UPMC, Neurobiologie des Processus Adaptatifs, 9 quai Saint Bernard, 75005, Paris, France
2 Institut fur Entwicklungsbiologie, Universität zu Köln, Gyrhofstr. 17, Köln, D-50931, Germany
3 CNRS UMR 144, Institut Curie, 75248 Paris Cedex 05, France
4 INSERM U440, Institut du Fer à Moulin - 17, rue du Fer à Moulin, 75005 Paris, France

* Corresponding author. E-mail address: sobel{at}ifm.inserm.fr.

Stathmin is a ubiquitous regulatory phosphoprotein, the generic element of a family of neural phosphoproteins in vertebrates which possess the capacity to bind Tubulin and interfere with microtubule dynamics. Although Stathmin and the other proteins of the family have been associated with numerous cell regulations, their biological roles remain elusive, as in particular inactivation of the stathmin gene in the mouse resulted in no clear deleterious phenotype. We identified Stathmin phosphoproteins in Drosophila, encoded by a unique gene sharing the intron/exon structure of the vertebrate stathmin and stathmin family genes. They interfere with microtubule assembly in vitro, and in vivo when expressed in HeLa cells. Drosophila Stathmin expression is regulated during embryogenesis: it is high in the migrating germ cells and in the central and peripheral nervous systems, a pattern resembling that of mammalian Stathmin. Furthermore, RNA interference inactivation of Drosophila Stathmin expression resulted in germ cell migration arrest at stage 14. It also induced important anomalies in nervous system development, such as loss of commissures and longitudinal connectives in the ventral cord, or abnormal chordotonal neuron organization. In conclusion, a single Drosophila gene encodes phosphoproteins homologous to the entire vertebrate Stathmin family. We demonstrate for the first time their direct involvement in major biological processes such as development of the reproductive and nervous systems.




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