Failure to express GAP-43 during neurogenesis affects cell cycle regulation and differentiation of neural precursors and stimulates apoptosis of neurons
S. Mani et al., Failure to express GAP-43 during neurogenesis affects cell cycle regulation and differentiation of neural precursors and stimulates apoptosis of neurons, MOL CELL NE, 17(1), 2001, pp. 54-66
GAP-43 is first expressed in proliferating neuroblasts and is required for
maturation of neurons. When GAP-43 is not expressed in differentiating embr
yonal carcinoma P19 cells, reduced numbers of neurons were generated. Here
we show that neuronal differentiation is initially disrupted at the onset o
f cell-cycle arrest in aggregated, proliferating neuronal precursors. The r
atio of nestin:beta -tubulin-labeled progeny generated at this stage sugges
ts that the differentiation is asymmetric. Apoptosis of immature neurons su
bsequently produced was also significantly induced. In vivo, too, prolifera
tion of neuroblasts was significantly reduced in cortex of GAP-43(-/-) mice
at E14.5. These data demonstrate that when GAP-43 is not expressed in prol
iferating neuroblasts, neural differentiation is not initiated appropriatel
y, inducing apoptosis. Moreover, the concurrent inhibition of Ca2+-dependen
t adhesion between differentiating P19 cells in aggregates implicates GAP-4
3 in CAM-mediated signaling during neurogenesis, as has been previously sho
wn in growth cones.