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
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.