EXPRESSION OF TIAM-1 IN THE DEVELOPING BRAIN SUGGESTS A ROLE FOR THE TIAM-1-RAC SIGNALING PATHWAY IN CELL-MIGRATION AND NEURITE OUTGROWTH

Citation
E. Ehler et al., EXPRESSION OF TIAM-1 IN THE DEVELOPING BRAIN SUGGESTS A ROLE FOR THE TIAM-1-RAC SIGNALING PATHWAY IN CELL-MIGRATION AND NEURITE OUTGROWTH, Molecular and cellular neurosciences, 9(1), 1997, pp. 1-12
Citations number
44
Categorie Soggetti
Neurosciences
ISSN journal
10447431
Volume
9
Issue
1
Year of publication
1997
Pages
1 - 12
Database
ISI
SICI code
1044-7431(1997)9:1<1:EOTITD>2.0.ZU;2-P
Abstract
During development proper neuronal migration and neurite extension are essential for the formation of functional neuronal networks. These pr ocesses require the reorganization of the cytoskeleton by modifying th e dynamics of actin filaments and microtubules. The Rho subfamily of G TPases regulates actin cytoskeletal changes during development. Tiam-1 , a GDP-GTP exchange factor for the small GTPase Rac and implicated in tumor invasion and metastasis, is expressed in the developing CNS. To study the function of Tiam-1 in neuronal migration and neurite extens ion, we examined the pattern of Tiam-1 expression in weaver mice, in w hich cerebellar granule cells fail to migrate to their final position and subsequently die. Tiam-1 is expressed in wild-type granule cells a s they migrate to the internal granular layer and send axons. In contr ast, weaver homozygous animals do not express Tiam-1 in premigratory g ranule cells. Heterozygous animals, in which granule cells exhibit a s low rate of migration, express low levels of Tiam-1. In the cerebral c ortex, Tiam-1 is also expressed in migrating neurons. Our findings sug gest that Tiam-1 contributes to cytoskeletal reorganization required d uring cell migration and neurite extension in defined neuronal populat ions, presumably by activation of Rac.