Inhibition of integrin-mediated adhesion and signaling disrupts retinal development.
Integrins are the major family of cell adhesion receptors that mediate cell adhesion to the extracellular matrix (ECM). Integrin-mediated adhesion and signaling play essential roles in neural development. In this study, we have used echistatin, an RGD-containing short monomeric disintegrin, to investigate the role of integrin-mediated adhesion and signaling during retinal development in Xenopus. Application of echistatin to Xenopus retinal-derived XR1 glial cells inhibited the three stages of integrin-mediated adhesion: cell attachment, cell spreading, and formation of focal adhesions and stress fibers. XR1 cell attachment and spreading increased tyrosine phosphorylation of paxillin, a focal adhesion associated protein, while echistatin significantly decreased phosphorylation levels of paxillin. Application of echistatin or beta(1) integrin function blocking antibody to the embryonic Xenopus retina disrupted retinal lamination and produced rosette structures with ectopic photoreceptors in the outer retina. These results indicate that integrin-mediated cell-ECM interactions play a critical role in cell adhesion, migration, and morphogenesis during vertebrate retinal development.
Li
Ming
M
Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50011, USA.
Sakaguchi
Donald S
DS
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D022502:Stress Fibers / Q000187:drug effects; D014981:Xenopus
D005353:Fibronectins; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; C057986:echistatin