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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
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The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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Cytoplasmic cyclin D1 modulates brain cortex development.

Neus Pedraza1, Daniel Rocandio2, Bahira Zammou2

  • 1Departmet of Basic Medical Sciences, Universitat de Lleida/Institut de Recerca Biomèdica de Lleida (IRBLLEIDA), Avda. Rovira Roure, 80, 25198, Lleida, Spain. neus.pedraza@udl.cat.

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Summary
This summary is machine-generated.

Cyclin D1 (CCND1) has a novel cytoplasmic role in brain development, independent of cell cycle regulation. This protein influences neuron progenitor detachment from the basement membrane, impacting cortical development.

Keywords:
End-feet adhesionIn utero electroporationNeuritogenesisNeuron migrationRadial glial cells

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • Proper timing of neuronal differentiation during nervous system development relies on cell cycle regulation and neurogenesis.
  • The molecular mechanisms governing the transition from cell cycle to neurogenesis are not fully understood.
  • Cyclins and cyclin-dependent kinases (CDKs) are key regulators of the cell cycle.

Purpose of the Study:

  • To investigate the function of cyclin D1 (CCND1) in cortex development.
  • To determine if CCND1 has roles beyond cell cycle regulation.
  • To elucidate the mechanisms by which CCND1 influences neurogenesis and cortical layering.

Main Methods:

  • Analysis of Ccnd1 knock-out embryos to observe cortical development.
  • In utero electroporation of dominant-negative CCND1 in neuron progenitors.
  • Immunofluorescence microscopy to determine CCND1 localization and its overlap with cellular markers like β1-integrin.
  • Examination of cell morphology and distribution of specific cell populations (TBR2+, CTIP2+).

Main Results:

  • CCND1 is found in the cytoplasm of radial glial processes (RGPs), particularly at the distal tip near the meningeal basement membrane, and associates with β1-integrin.
  • Ccnd1 knock-out embryos exhibit abnormal cortical layering and altered distribution of TBR2+ and CTIP2+ cells, without affecting proliferation.
  • Overexpression of a dominant-negative CCND1 recapitulates some of these cellular defects, suggesting a cytoplasmic, cell-cycle-independent function.
  • Cytoplasmic CCND1 influences neuron morphology and is crucial for RGP detachment from the basement membrane via paxillin phosphorylation.

Conclusions:

  • CCND1 possesses a significant cytoplasmic function in cortical development that is separate from its role in cell cycle regulation.
  • Cytoplasmic CCND1 is essential for the proper detachment of neural progenitors from the meningeal basement membrane.
  • This study reveals a novel non-canonical function of CCND1 in regulating neurogenesis and brain development.