Expression ofTiam-1in the Developing Brain Suggests a Role for the Tiam-1–Rac Signaling Pathway in Cell Migration and Neurite Outgrowth

Abstract

During development proper neuronal migration and neurite extension are essential for the formation of functional neuronal networks. These processes require the reorganization of the cytoskeleton by modifying the dynamics of actin filaments and microtubules. The Rho subfamily of GTPases 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 extension, we examined the pattern ofTiam-1expression inweavermice, in which cerebellar granule cells fail to migrate to their final position and subsequently die.Tiam-1is expressed in wild-type granule cells as they migrate to the internal granular layer and send axons. In contrast,weaverhomozygous animals do not expressTiam-1in premigratory granule cells. Heterozygous animals, in which granule cells exhibit a slow rate of migration, express low levels ofTiam-1.In the cerebral cortex,Tiam-1is also expressed in migrating neurons. Our findings suggest that Tiam-1 contributes to cytoskeletal reorganization required during cell migration and neurite extension in defined neuronal populations, presumably by activation of Rac.