RETROVIRALLY INTRODUCED ANTISENSE INTEGRIN RNA INHIBITS NEUROBLAST MIGRATION INVIVO

We used retrovirus-mediated gene transfer to ask whether integrins are involved in the development of neuroblasts in the chicken optic tectum. Vectors were constructed with the E. coli lacZ gene in the sense orientation and beta1 integrin sequences in the antisense orientation. Tests in culture showed that the progeny of cells infected by these vectors were identifiable by expression of LacZ and had reduced levels of beta1 integrins on their surfaces. We then injected these vectors into optic tecta on E3, at the height of neuronal production. Clones of LacZ-positive cells were analyzed 3-9 days later, as they migrated along radial glia to form the tectal plate. Antisense sequences had little effect on the proliferation of progenitors, or on the radial stacking of their progeny in the ventricular zone (E6). However, many antisense-bearing cells accumulated in the ventricular zone and failed to migrate into the tectal plate (E7.5 and E9). At later stages (E12), few antisense-bearing cells could be found. Thus, integrin appears to be required in the migratory process, and cells that fail to engage in integrin-mediated interactions may die.