Integrin alpha4beta1 function is required for cell survival in developing retina

TitleIntegrin alpha4beta1 function is required for cell survival in developing retina
Publication TypeJournal Article
Year of Publication2004
AuthorsLeu ST, Jacques SAL, Wingerd KL, Hikita ST, Tolhurst EC, Pring JL, Wiswell D, Kinney L, Goodman NL, Jackson DY, Clegg DO
JournalDevelopmental Biology
Date Published2004 Dec 15
KeywordsAnimals, Apoptosis, Cell Shape, Cell Survival, Chick Embryo, Genetic Vectors, Humans, In Situ Hybridization, In Situ Nick-End Labeling, Integrin alpha4beta1, Neurons, Protein Subunits, Retina, Vascular Cell Adhesion Molecule-1

In the retina, integrins in the beta1 family have been shown to be important in many phases of neuronal development, particularly neuroblast migration and axon outgrowth. However, the functions of specific integrin heterodimers are not well defined. In this study, we investigated the functions of beta1 integrins in developing chicken retina by expression of a dominant-negative beta1A construct using a replication-competent retrovirus. Inhibition of integrins using this approach resulted in alteration of cell morphology and increased apoptosis, but did not preclude migration and axon elongation. In an attempt to identify which specific beta1 heterodimer was important, expression and function of the alpha4beta1 heterodimer were also investigated. At early developmental stages, alpha4 protein and mRNA were detected in undifferentiated neuroblasts throughout the retina. At later stages, expression was confined to retinal ganglion cells (RGCs) and amacrine cells. A small molecule antagonist of alpha4 integrins was shown to inhibit neurite outgrowth on recombinant soluble vascular cell adhesion molecule-1 (VCAM-1), a known ligand of alpha4beta1. Introduction of alpha4 antagonist in vivo gave rise to increased apoptosis and led to a thinning of the retina and reduced numbers of retinal ganglion cells (RGCs). We conclude that the integrin alpha4beta1 is important for survival of developing retinal neurons, including RGCs.

Alternate JournalDev. Biol.
PubMed ID15581875
Grant ListEY09736 / EY / NEI NIH HHS / United States