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Updated: Sep 3, 2025
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2D and 3D Human Induced Pluripotent Stem Cell-Based Models to Dissect Primary Cilium Involvement during Neocortical Development
Published on: March 25, 2022
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Ciliogenesis requires sphingolipid-dependent membrane and axoneme interaction
Dou Wu1,2,3,4, Jingying Huang1,2,3,4, Hao Zhu1,2,3,4
1Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
Summary
Sphingolipids are crucial for cilium formation and regeneration. Disruptions in sphingolipid production, like serine palmitoyltransferase (SPT) deficiencies, lead to ciliopathies, but can be restored with supplementation.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cilium formation and regeneration depend on protein synthesis, but the regulation of cytosolic translation during this process is poorly understood.
- Understanding translational control is key to deciphering ciliogenesis mechanisms.
Purpose of the Study:
- To investigate the global translational reprogramming during cilia regeneration in *Chlamydomonas*.
- To identify key regulators of ciliogenesis by analyzing translatome profiles.
- To elucidate the role of sphingolipids in cilium structure and function.
Main Methods:
- Ribosome footprinting for global translatome profiling.
- Cryo-electron tomography for structural analysis of cilia.
- Analysis of serine palmitoyltransferase (SPT) deficient cells and patient-derived mutations.
Main Results:
- Flagellar genes show early transcriptional activation but late translational repression during cilia regeneration.
- Sphingolipid metabolism enzymes, including SPT, are essential for ciliogenesis.
- Ceramide loss leads to increased membrane-axoneme distance and abnormal cilia morphology.
- Ceramides interact with intraflagellar transport (IFT) machinery, connecting the ciliary membrane to the axoneme.
- SPT deficiency in vertebrate cells and patient mutations impair ciliogenesis, which is reversible with sphingolipid supplementation.
Conclusions:
- Sphingolipids play a conserved and essential role in cilium formation and maintenance.
- The study links impaired sphingolipid production to ciliopathies.
- Restoration of sphingolipid levels can rescue ciliary defects.
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