Failure to express GAP-43 during neurogenesis affects cell cycle regulation and differentiation of neural precursors and stimulates apoptosis of neurons

Citation
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
Citations number
56
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
MOLECULAR AND CELLULAR NEUROSCIENCE
ISSN journal
1044-7431 → ACNP
Volume
17
Issue
1
Year of publication
2001
Pages
54 - 66
Database
ISI
SICI code
1044-7431(200101)17:1<54:FTEGDN>2.0.ZU;2-H
Abstract
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.