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Evaluation of Planar-Cell-Polarity Phenotypes in Ciliopathy Mouse Mutant Cochlea
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FBW7 couples structural integrity with functional output of primary cilia

Eleni Petsouki1, Vasileios Gerakopoulos1, Nicholas Szeto2

  • 1Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Communications Biology
|September 14, 2021
PubMed

Insights

FBW7 regulates primary cilia length and mesenchymal stem cell differentiation. It controls ciliogenesis regulators, impacting bone formation and Hedgehog pathway activity, crucial for stem cell function.

Area of Science:

  • Cell Biology
  • Stem Cell Biology
  • Biochemistry

Background:

  • Primary cilia structural defects impact diverse tissues.
  • The functional outcomes of ciliary length disorders remain unclear.
  • Understanding ciliary length control mechanisms is vital for stem cell differentiation.

Purpose of the Study:

  • To investigate the role of FBW7-mediated NDE1 destruction in controlling primary cilia length.
  • To examine the impact of this mechanism on mesenchymal stem cell (MSC) differentiation.
  • To elucidate the relationship between ciliary structure, Hedgehog pathway activity, and bone development.

Main Methods:

  • Utilized genetic manipulation (e.g., Fbxw7 deletion) in mesenchymal stem cells.
  • Assessed primary cilia formation, length, and associated signaling pathways (Hedgehog).
  • Analyzed MSC differentiation into osteoblasts and effects on bone architecture.

Main Results:

  • FBW7 acts as a master regulator of ciliogenesis, positively influencing cilia formation and MSC osteogenic differentiation.
  • FBW7 deletion impairs ciliation and Hedgehog activity, with partial rescue in Fbxw7/Nde1-null cells.
  • NDE1 suppresses ciliogenesis but promotes MSC differentiation via cilia-independent Hedgehog pathway activation.

Conclusions:

  • FBW7 integrates ciliary structure and function through a protein-protein interaction network essential for stem cell differentiation.
  • This network is critical for regulating primary cilia length and downstream signaling pathways.
  • The findings provide insights into mechanisms governing stem cell fate and bone development.

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