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Development of mice expressing a single D-type cyclin

Maria A Ciemerych1, Anna M Kenney, Ewa Sicinska

  • 1Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Genes & Development
|December 28, 2002
PubMed

Insights

The three D-cyclins (D1, D2, D3) are interchangeable in early development. However, later, single-cyclin mice show distinct organ defects and premature death due to failed cyclin D upregulation.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • D-cyclins (cyclin D1, D2, D3) are crucial for cell cycle progression.
  • Their specific roles in driving lineage development remain incompletely understood.

Purpose of the Study:

  • To investigate the functional redundancy and tissue-specific requirements of D-cyclins.
  • To determine if D-cyclin functions are interchangeable during mammalian development.

Main Methods:

  • Generation of "single-cyclin" mice expressing only one of the three D-cyclins.
  • Analysis of embryonic development and adult phenotypes in these genetically modified mice.
  • Examination of gene expression and protein levels in affected tissues.

Main Results:

  • Single-D-cyclin embryos develop normally until late gestation, indicating functional exchangeability at this stage.
  • Adult single-cyclin mice exhibit distinct abnormalities: cyclin D1-only mice develop anemia, cyclin D2-only mice show neurological deficits, and cyclin D3-only mice have cerebellar defects.
  • Affected tissues in single-cyclin mice failed to up-regulate the remaining D-cyclin, suggesting compartment-specific regulatory mechanisms.

Conclusions:

  • D-cyclin functions are largely redundant during early embryonic development.
  • Tissue-specific requirements for particular D-cyclins in later life arise from the inability to up-regulate them in specific cell types.
  • Transcription factors, such as N-myc in cerebellar granule neuron precursors, dictate the requirement for specific D-cyclins, rather than unique cyclin properties.

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