INTEGRIN ALPHA-6 EXPRESSION IS REQUIRED FOR EARLY NERVOUS-SYSTEM DEVELOPMENT IN XENOPUS-LAEVIS

The integrin alpha 6 subunit pairs with both the beta 1 and beta 4 sub units to form a subfamily of laminin receptors, Here we report the cDN A cloning and primary sequence for the Xenopus homologue of the mammal ian integrin alpha 6 subunit. We present data demonstrating the spatia l and temporal expression of alpha 6 mRNA and protein during early dev elopment. Initially, alpha 6 transcripts are expressed in the dorsal e ctoderm and future neural plate at the end of gastrulation, Later in d evelopment, alpha 6 mRNAs are expressed in a variety of neural derivat ives, including the developing sensory placodes (otic and olfactory) a nd commissural neurons within the neural tube, lntegrin alpha 6 is als o expressed in the elongating pronephric duct as well as a subset of t he rhombencephalic neural crest, which will form the Schwann cells lin ing several cranial nerves (VII, VIII and X), In vivo expression of an alpha 6 antisense transcript in the animal hemisphere leads to a redu ction in alpha 6 protein expression, a loss of adhesion to laminin, an d severe defects in normal development, In 35% of cases, reduced level s of alpha 6 expression result in embryos that complete gastrulation n ormally but arrest at neurulation prior to the formation of the neural plate, In an additional 22% of cases, embryos develop with severe axi al defects, including complete loss of head or tail structures, In con trast, overexpression of the alpha 6 subunit by injection of full-leng th mRNA has no apparent effect on embryonic development, Go-injection of antisense and sense plasmid constructs results in a partial rescue of the antisense-generated phenotypes. These data indicate that the in tegrin alpha 6 subunit is critical for the early development of the ne rvous system in amphibians.