Integrin receptors are required for cell survival and proliferation during development of the peripheral glial lineage

Abstract

Proliferation and survival of Schwann cells are important for nerve development and for disease processes in peripheral nerves. We have analyzed embryos lacking α4- or α5-integrins and show here that these integrins contribute to the control of glial cell numbers. To overcome early embryonic lethality an explant and grafting system that allows the study of isolated glial progenitor cells both in vitro and in vivo was used. Schwann cells differentiate in the absence of α5 but their numbers and the proliferation rate of early progenitor cells are reduced, suggesting that α5 is essential for normal proliferation. Survival, rather than proliferation, is compromised in α4-deficient explants. Conditional immortalization allowed further characterization and revealed that α4 contributes to survival in a cell-density-dependent fashion. In addition, transplants into chicken embryos were used to analyze in vivo cell migration and showed that cell death occurs mainly in highly motile, individually migrating cells. The cell death patterns in vitro and in vivo argue that α4-integrins play a role in survival during cell migration. Neural crest migration has been suggested to require these integrins; however, no defects in migration were observed in the absence of α4 or α5. We conclude that integrins can complement growth factors in the control of glial cell numbers. © 2001 Academic Press.