The alpha 6 integrin is essential for early nervous system development in Xenopus laevis. We have previously reported a uPA cleaved form of integrin alpha 6 (alpha 6p), in invasive human prostate cancer tissue, whose presence correlates with increased migration and invasive capacity. We now report that alpha 6 is cleaved during the normal development of Xenopus in a spatially and temporally controlled manner. In addition, unlike normal mammalian tissues, which lack alpha 6p, the major form of the alpha 6 integrin present in adult Xenopus is alpha 6p. The protease responsible for the cleavage in mammals, uPA, is not involved in the cleavage of Xenopus alpha 6. Finally, overexpression of a mammalian alpha 6 mutant which cannot be cleaved leads to developmental abnormalities suggesting a potential role for the cleavage in development. (c) 2007 Elsevier Inc. All rights reserved.