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Journal of Neuroscience, Vol 16, 210-219, Copyright © 1996 by Society for Neuroscience
MN20, a D2 cyclin, is transiently expressed in selected neural populations during embryogenesis
ME Ross, ML Carter and JH Lee
Department of Neurology, University of Minnesota, Minneapolis 55455, USA.
Although the regulation of proliferation and differentiation during brain
development has long been considered to be interrelated, the mechanisms
that coordinate the control of cell division and histogenesis are poorly
understood. The cell cycle is a dynamic process that is governed by the
concerted action of numerous cell cycle regulatory proteins in response to
signals both intrinsic and extrinsic to the cell. Thus, proteins that
regulate the cell cycle are well suited to provide a link between processes
that control neuroblast proliferation and differentiation. We reported
previously the isolation from brain of a message form of D2 cyclin, one of
several cyclin proteins known to promote the progression from G1 to S
phase. This MN20/D2 cyclin mRNA is expressed in highly restricted neural
populations at embryonic (E) day 15 and postnatal (P) day 6 in the mouse.
To gain insight into the role(s) this cyclin may serve in brain formation,
the spatial and temporal pattern of MN20/D2 cyclin expression was examined
by in situ hybridization at 48 hr intervals from E10.5 to P8. MN20 mRNA was
detected in developing cerebellum, dorsal mesencephalon, cerebral cortex,
and epithalamus, but not hippocampus, striatum, or thalamus. Comparison
with 5-bromodeoxyuridine labeling of cells in S phase indicated that MN20
expression in embryonic cerebellum and cerebral cortex was most pronounced
in young neurons that recently had become postmitotic. Although expressed
in other embryonic cerebellar neurons, MN20 was detected in granule
precursors only postnatally, after their migration from the rhombic lip to
the external germinal layer. This indicates that MN20/D2 cyclin is induced
in cerebellar granule precursors as they become competent to differentiate.
The spatial distribution of MN20 expression in the developing brain
suggests that regional differences in cell cycle regulation depend in part
on the selective use of cyclin proteins. Moreover, detection of MN20 mRNA
in postmitotic neural cells indicates that cyclin D2 expression has effects
beyond promoting cell cycle progression and may also have a role in the
response of the neural precursor to terminal differentiation signals as the
cells exits from proliferation.
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