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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
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Transient Primary Cilia Mediate Robust Hedgehog Pathway-Dependent Cell Cycle Control.

Emily K Ho1, Anaïs E Tsai2, Tim Stearns3

  • 1Department of Developmental Biology, Stanford School of Medicine, Stanford, CA 94305, USA.

Current Biology : CB
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Hedgehog (Hh) signaling regulates proliferation via primary cilia. Even though cilia are transient, Hh pathway activity robustly controls cell proliferation, persisting across cell cycles.

Keywords:
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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Signaling

Background:

  • Hedgehog (Hh) signaling is crucial for developmental proliferation.
  • Primary cilia are essential for Hh signal transduction.
  • Primary cilia are transient organelles, often absent during proliferation.

Purpose of the Study:

  • Investigate how transient primary cilia mediate Hh signaling for proliferation.
  • Clarify the role of primary cilia in Hh pathway activity during the cell cycle.

Main Methods:

  • Utilized a mouse medulloblastoma cell line (SMB55) dependent on Hh signaling.
  • Employed live imaging to track primary cilia presence and Hh pathway activity across multiple cell cycles.
  • Analyzed the role of cyclin D1 in pathway persistence.

Main Results:

  • SMB55 cells and cerebellar granule neuron precursors (GNPs) possess primary cilia beyond G1 into S phase.
  • Primary cilium presence dictates Hh pathway activity periods.
  • Hh pathway activity in preceding or current G1 is sufficient for cell cycle entry.
  • Cyclin D1 mediates persistent Hh pathway effects.

Conclusions:

  • Hh pathway control of proliferation is robust despite primary cilium transience.
  • Primary cilium dynamics may influence other Hh-mediated developmental events.