Inhibition of Neural Crest Cell Attachment by Integrin Antisense Oligonucleotides

Neural crest cell interactions with extracellular matrix molecules were analyzed with the use of antisense oligonucleotides to block synthesis of integrin subunits. When added to the culture medium of quail neural crest cells, selected antisense phosphorothiol oligonucleotides reduced the amounts of cell surface alpha 1 or beta 1 integrin subunits by up to 95 percent and inhibited neural crest cell attachment to laminin or fibronectin substrata. Differential effects on specific alpha integrins were noted after treatment with alpha-specific oligonucleotides. Cells recovered the ability to bind to substrata 8 to 16 hours after treatment with inhibitory oligonucleotides. The operation of at least three distinct alpha integrin subunits is indicated by substratum-selective inhibition of cell attachment.