Essential role for cyclin D3 in granulocyte colony-stimulating factor-driven expansion of neutrophil granulocytes

Ewa Sicinska, Young Mi Lee, Judith Gits, Hirokazu Shigematsu, Qunyan Yu, Vivienne I. Rebel, Yan Geng, Christopher J. Marshall, Koichi Akashi, David M. Dorfman, Ivo P. Touw, Piotr Sicinski

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


The proliferation of neutrophil granulocyte lineage is driven largely by granulocyte colony-stimulating factor (G-CSF) acting via the G-CSF receptors. In this study, we show that mice lacking cyclin D3, a component of the core cell cycle machinery, are refractory to stimulation by the G-CSF. Consequently, cyclin D3-null mice display deficient maturation of granulocytes in the bone marrow and have reduced levels of neutropliil granulocytes in their peripheral blood. The mutant mice are unable to mount a normal response to bacterial challenge and succumb to microbial infections. In contrast, the expansion of hematopoietic stem cells and lineage-committed myeloid progenitors proceeds relatively normally in mice lacking cyclin D3, revealing that the requirement for cyclin D3 function operates at later stages of neutrophil development. Importantly, we verified that this requirement is specific to cyclin D3, as mice lacking other G1 cyclins (D1, D2, E1, or E2) display normal granulocyte counts. Our analyses revealed that in the bone marrow cells of wild-type mice, activation of the G-CSF receptor leads to upregulation of cyclin D3. Collectively, these results demonstrate that cyclin D3 is an essential cell cycle recipient of G-CSF signaling, and they provide a molecular link of how G-CSF-dependent signaling triggers cell proliferation.

Original languageEnglish (US)
Pages (from-to)8052-8060
Number of pages9
JournalMolecular and cellular biology
Issue number21
StatePublished - Nov 2006
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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