Wild-type and mutant forms of v-src differentially alter neuronal migration and differentiation in vivo.
The effects of three different forms of v-src on brain cell development were determined in vivo. Recombinant retroviral vectors encoding the marker lacZ (control) and either wild-type v-src or SH2 or SH3 domain-deleted forms of v-src (deltaSH2 or deltaSH3, respectively) were used to infect neuronal progenitor cells in the embryonic chicken midbrain (optic tectum; OT). Embryos were injected in the OT with retroviral concentrates on embryonic day (E) 3 and sacrificed at E6, E9, and later in development. Patterns of cell proliferation, migration, and differentiation of lacZ-marked clonal cell progeny were then analyzed. Relative to lacZ-only controls, cell clone size at E6 was significantly increased for v-src-, unchanged for deltaSH2-, and smaller for deltaSH3-injected embryos. At E9, deltaSH2 cell clones were significantly larger than controls, suggesting increased survival from normal programmed cell death. Radial neuronal migration was impaired for v-src and deltaSH3 clones, whereas tangential neuronal migration was enhanced along fiber tracts in v-src and deltaSH2 clones. Moreover, radial glial cell development and differentiation was hindered in v-src and deltaSH3 clones. These experiments demonstrate that ectopic v-src signaling alters proliferation, migration, survival, and differentiation of developing brain cells and suggest that src signaling pathways are involved in these developmental processes. Furthermore, certain effects of v-src on brain cells require specific src homology domains.
Morgan
J C
JC
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta 30912-2000, USA.
Majors
J E
JE
Galileo
D S
DS
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000502:physiology*; D002642:Chick Embryo; D002999:Clone Cells; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D016391:Genes, src / Q000235:genetics*; D005822:Genetic Vectors; D016296:Mutagenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000201:enzymology / Q000821:virology; D010641:Phenotype; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012190:Retroviridae; D015398:Signal Transduction / Q000235:genetics; D013477:Superior Colliculi / Q000166:cytology; D018909:src Homology Domains / Q000235:genetics
D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases