Retroviral transfer of antisense integrin α6 or α8 sequences results in laminar redistribution or clonal cell death in developing brain

Abstract

To assess the roles of two integrin α subunits (α6 and α8) in the developing chicken optic rectum, progenitors were infected with retroviral vectors that contained the marker gene lacZ plus antisense sequences from either the α6 or α8 integrin subunit cDNAs. On embryonic day 3 (E3), the vector was injected into rectal ventricles of chicken embryos. On E6, E7.5, E9, or later, chicken embryos were killed, and optic tecta were dissected and processed for histochemical detection of lacZ-positive cells. The antisense- bearing cell clones (descendants of a single infected progenitor) were analyzed for proliferation and migration patterns and were compared with lacZ-only vectorinfected control clones. At E6, both α6 and α8 integrin antisense-containing cell clones were similar to controls. At E7.5, integrin α8 antisense-containing clones exhibited a cell number reduction in upper laminae (intermediate zone and tectal plate), and at E9, they exhibited a reduction in the ventricular zone as well. Integrin α6 antisense-containing cell clones exhibited no difference in total cell number at E9 but had a net laminar redistribution of more cells in the ventricular zone and less cells in the tectal plate. Our data show that different integrins play different roles during brain development: α6 integrin is essential for migration of rectal cells into specific laminae, and α8 integrin is essential for the survival of optic rectum cells. Also α8 integrin-substrate interactions may suppress early programmed cell death in premigratory and migratory neuroblasts.