Abstract
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.
