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J. Cell Biol.,
Volume 140, Number 6, March 23, 1998 1497-1509
Center for Neuronal Survival, Montreal Neurological Institute, McGill University, 3801 rue University, Montreal, Canada H3A 2B4
In this report, we have examined the requirement for the retinoblastoma (Rb) gene family in neuronal determination with a focus on the developing
neocortex. To determine whether pRb is required for
neuronal determination in vivo, we crossed the Rb
/ mice with transgenic mice expressing 
-galactosidase
from the early, panneuronal T
1 -tubulin promoter
(T1:nlacZ). In E12.5 Rb/ embryos, the T1:nlacZ
transgene was robustly expressed throughout the developing nervous system. However, by E14.5, there were
perturbations in T1:nlacZ expression throughout the
nervous system, including deficits in the forebrain and
retina. To more precisely define the temporal requirement for pRb in neuronal determination, we functionally ablated the pRb family in wild-type cortical progenitor cells that undergo the transition to postmitotic neurons in vitro by expression of a mutant adenovirus
E1A protein. These studies revealed that induction of
T1:nlacZ did not require proteins of the pRb family.
However, in their absence, determined, T1:nlacZ-positive cortical neurons underwent apoptosis, presumably as a consequence of "mixed signals" deriving from their
inability to undergo terminal mitosis. In contrast, when
the pRb family was ablated in postmitotic cortical neurons, there was no effect on neuronal survival, nor did it
cause the postmitotic neurons to reenter the cell cycle.
Together, these studies define a critical temporal window of requirement for the pRb family; these proteins are not required for induction of neuronal gene expression or for the maintenance of postmitotic neurons, but
are essential for determined neurons to exit the cell cycle and survive.
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