Integrin α6 expression is required for early nervous system development in Xenopus laevis

The integrin α6 subunit pairs with both the β1 and β4 subunits to form a subfamily of laminin receptors. Here we report the cDNA cloning and primary sequence for the Xenopus homologue of the mammalian integrin α6 subunit. We present data demonstrating the spatial and temporal expression of α6 mRNA and protein during early development. Initially, α6 transcripts are expressed in the dorsal ectoderm and future neural plate at the end of gastrulation. Later in development, α6 mRNAs are expressed in a variety of neural derivatives, including the developing sensory placodes (otic and olfactory) and commissural neurons within the neural tube. Integrin α6 is also expressed in the elongating pronephric duct as well as a subset of the rhombencephalic neural crest, which will form the Schwann cells lining several cranial nerves (VII, VIII and X). In vivo expression of an α6 antisense transcript in the animal hemisphere leads to a reduction in α6 protein expression, a loss of adhesion to laminin, and severe defects in normal development. In 35% of cases, reduced levels of α6 expression result in embryos that complete gastrulation normally but arrest at neurulation prior to the formation of the neural plate. In an additional 22% of cases, embryos develop with severe axial defects, including complete loss of head or tail structures. In contrast, overexpression of the α6 subunit by injection of full-length mRNA has no apparent effect on embryonic development. Co-injection of antisense and sense plasmid constructs results in a partial rescue of the antisense-generated phenotypes. These data indicate that the integrin α6 subunit is critical for the early development of the nervous system in amphibians.