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The Journal of Neuroscience, September 1, 1998, 18(17):6928-6938

Retroviral Transfer of Antisense Integrin 6 or 8 Sequences Results in Laminar Redistribution or Clonal Cell Death in Developing Brain

Zhiqiang Zhang and Deni S. Galileo

Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia 30912-2000

To assess the roles of two integrin  subunits (6 and 8) in the developing chicken optic tectum, progenitors were infected with retroviral vectors that contained the marker gene lacZ plus antisense sequences from either the 6 or 8 integrin subunit cDNAs. On embryonic day 3 (E3), the vector was injected into tectal 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 vector-infected control clones. At E6, both 6 and 8 integrin antisense-containing cell clones were similar to controls. At E7.5, integrin 8 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 6 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: 6 integrin is essential for migration of tectal cells into specific laminae, and 8 integrin is essential for the survival of optic tectum cells. Also 8 integrin-substrate interactions may suppress early programmed cell death in premigratory and migratory neuroblasts.

Key words: integrin; antisense; neuronal migration; apoptosis; retroviral vector; chicken embryo

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18176928-11$05.00/0

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