RETROVIRAL TRANSFER OF ANTISENSE INTEGRIN ALPHA-6 OR ALPHA-8 SEQUENCES RESULTS IN LAMINAR REDISTRIBUTION OR CLONAL CELL-DEATH IN DEVELOPINGBRAIN

To assess the roles of two integrin alpha subunits (alpha 6 and alpha 8) in the developing chicken optic tectum, progenitors were infected w ith retroviral vectors that contained the marker gene lacZ plus antise nse sequences from either the alpha 6 or alpha 8 integrin subunit cDNA s. On embryonic day 3 (E3), the vector was injected into tectal ventri cles of chicken embryos. On E6, E7.5, E9, or later, chicken embryos we re killed, and optic tecta were dissected and processed for histochemi cal detection of lacZ-positive cells. The antisense-bearing cell clone s (descendants of a single infected progenitor) were analyzed for prol iferation and migration patterns and were compared with lacZ-only vect or-infected control clones. At E6, both alpha 6 and alpha 8 integrin a ntisense-containing cell clones were similar to controls. At E7.5, int egrin alpha 8 antisense-containing clones exhibited a cell number redu ction in upper laminae (intermediate zone and tectal plate), and at E9 , they exhibited a reduction in the ventricular zone as well. Integrin alpha 6 antisense-containing cell clones exhibited no difference in t otal cell number at E9 but had a net laminar redistribution of more ce lls in the ventricular zone and less cells in the tectal plate. Our da ta show that different integrins play different roles during brain dev elopment: alpha 6 integrin is essential for migration of tectal cells into specific laminae, and alpha 8 integrin is essential for the survi val of optic tectum cells. Also alpha 8 integrin-substrate interaction s may suppress early programmed cell death in premigratory and migrato ry neuroblasts.