Wild-type and mutant forms of v-src differentially alter neuronal migration and differentiation in vivo

John Christopher Morgan, John E. Majors, Deni S. Galileo

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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 (ΔSH2 or ΔSH3, 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 ΔSH2-, and smaller for ΔSH3-injected embryos. At E9, ΔSH2 cell clones were significantly larger than controls, suggesting increased survival from normal programmed cell death. Radial neuronal migration was impaired for v-src and ΔSH3 clones, whereas tangential neuronal migration was enhanced along fiber tracts in v-src and ΔSH2 clones. Moreover, radial glial cell development and differentiation was hindered in v-src and ΔSH3 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.

Original languageEnglish (US)
Pages (from-to)226-237
Number of pages12
JournalJournal of Neuroscience Research
Volume59
Issue number2
DOIs
StatePublished - Jan 15 2000

Keywords

  • Chick embryo
  • Optic tectum
  • Retroviral vector
  • Tyrosine kinase
  • V-src

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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