K. Schlett et E. Madarasz, RETINOIC ACID-INDUCED NEURAL DIFFERENTIATION IN A NEUROECTODERMAL CELL-LINE IMMORTALIZED BY P53 DEFICIENCY, Journal of neuroscience research, 47(4), 1997, pp. 405-415
Neuroepithelial cell lines were established from cerebral vesicles of
9-day-old mouse embryos lacking functional p53 genes (Livingstone et a
l: Cell 70:923-935, 1992). All-trans retinoic acid (RA) induced bulk f
ormation of neurons both in several p53-deficient neuroepithelial cell
lines and in wild-type neural cells derived from early embryonic (E9-
E12) forebrain vesicles. Forty-eight-hour treatment with 10(-6) M RA w
as necessary and sufficient to initiate neuron formation by p53(-/-)-p
rogenitors, but neuronal characteristics appeared with a delay of 3-4
days. The first appearance of cells with astroglial features followed
that of neurons with a further delay of 4-5 days. The establishment of
neuronal phenotypes involved minimally three rounds of cell cycle. Fu
ture neurons were sorted out from substrate-attached cells and were ch
aracterized by a specific rearrangement of nestin-immunoreactive filam
ents. The formation of neuronal phenotypes was not synchronized within
the RA-treated cell populations. The data indicate that RA, which pro
motes the initiation of neural differentiation, cannot function as a d
irect regulator of cell-fate decisions made by neural progenitor cells
. (C) 1997 Wiley-Liss, Inc.