Cerebellar histogenesis is disturbed in mice lacking cyclin D2.
Formation of brain requires deftly balancing primary genesis of neurons and glia, detection of when sufficient cells of each type have been produced, shutdown of proliferation and removal of excess cells. The region and cell type-specific expression of cell cycle regulatory proteins, such as demonstrated for cyclin D2, may contribute to these processes. If so, regional brain development should be affected by alteration of cyclin expression. To test this hypothesis, the representation of specific cell types was examined in the cerebellum of animals lacking cyclin D2. The loss of this cyclin primarily affected two neuronal populations: granule cell number was reduced and stellate interneurons were nearly absent. Differences between null and wild-type siblings were obvious by the second postnatal week. Decreases in granule cell number arose from both reduction in primary neurogenesis and increase in apoptosis of cells that fail to differentiate. The dearth of stellate cells in the molecular layer indicates that emergence of this subpopulation requires cyclin D2 expression. Surprisingly, Golgi and basket interneurons, thought to originate from the same precursor pool as stellate cells, appear unaffected. These results suggest that cyclin D2 is required in cerebellum not only for proliferation of the granule cell precursors but also for proper differentiation of granule and stellate interneurons.
Huard
J M
JM
Laboratory of Molecular Neurobiology and Development, Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA.
Forster
C C
CC
Carter
M L
ML
Sicinski
P
P
Ross
M E
ME
D000375:Aging; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D002531:Cerebellum / Q000196:embryology* / Q000254:growth & development* / Q000473:pathology; D003433:Crosses, Genetic; D056742:Cyclin D2; D016213:Cyclins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D007395:Interneurons / Q000166:cytology / Q000473:pathology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000473:pathology / Q000502:physiology*
C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D009419:Nerve Tissue Proteins