Jc. Morgan et al., Wild-type and mutant forms of v-sre differentially alter neuronal migration and differentiation in vivo, J NEUROSC R, 59(2), 2000, pp. 226-237
The effects of three different forms of v-src on brain cell development wer
e determined in vivo. Recombinant retroviral vectors encoding the marker la
cZ (control) and either wild-type v-src or SH2 or SH3 domain-deleted forms
of v-src (Delta SH2 or Delta SH3, respectively) were used to infect neurona
l progenitor cells in the embryonic chicken midbrain (optic tectum; OT). Em
bryos 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 p
rogeny were then analyzed. Relative to lacZ-only controls, cell clone size
at E6 was significantly increased for v-src-, unchanged for Delta SH2-, and
smaller for Delta SH3-injected embryos. At E9, Delta SH2 cell clones were
significantly larger than controls, suggesting increased survival from norm
al programmed cell death. Radial neuronal migration was impaired for v-src
and Delta SH3 clones, whereas tangential neuronal migration was enhanced al
ong fiber tracts in v-src and Delta SH2 clones. Moreover, radial glial cell
development and differentiation was hindered in v-src and Delta SH3 clones
. These experiments demonstrate that ectopic v-src signaling alters prolife
ration, 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 sp
ecific src homology domains. (C) 2000 Wiley-Liss, Inc.