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Wild‐type and mutant forms of v‐src differentially alter neuronal migration and differentiation in vivo
Author(s) -
Morgan John C.,
Majors John E.,
Galileo Deni S.
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(20000115)59:2<226::aid-jnr9>3.0.co;2-j
Subject(s) - proto oncogene tyrosine protein kinase src , biology , microbiology and biotechnology , embryonic stem cell , progenitor cell , cell migration , cellular differentiation , clone (java method) , signal transduction , cell , stem cell , genetics , gene
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. J. Neurosci. Res. 59:226–237, 2000 © 2000 Wiley‐Liss, Inc.