Dissecting the functional interplay between the TOR pathway and the cilium in zebrafish
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Updated: May 13, 2026
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Published on: April 2, 2016
Shiaulou Yuan1, Lu Zhao, Zhaoxia Sun
1Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Abstract:
The target-of-rapamycin (TOR) pathway is a major regulator of cellular growth, division, and metabolism by coupling growth and nutrient cues to fundamental processes such as translation and transcription. In vertebrate models, disruptions affecting components of the TOR pathway result in cilia size abnormalities and ciliopathic phenotypes such as renal cysts. However, the mechanism by which the TOR pathway influenced cilia length and function was unknown. Recent work from zebrafish, in conjunction with the green alga Chlamydomonas, demonstrates that TOR complex 1 (TORC1)-mediated cilia length control is achieved through translational regulation of ciliary precursors. Further, in zebrafish, aberrant TORC1 signaling leads to left-right asymmetric patterning defects due to inefficient ciliary motility and fluid flow generation in the Kupffer's vesicle, a conserved embryonic organ that establishes laterality. Together, such findings show the utility of a combinatorial zebrafish and Chlamydomonas approach to dissecting the mechanistic relationship between the cilium and signaling molecules such as TOR. Here, we describe tools, reagents, and methodologies for the manipulation of the TOR pathway and the analysis of cilia morphology and function in zebrafish and Chlamydomonas.
Insights
The target-of-rapamycin (TOR) pathway regulates cell growth and metabolism. New research shows TOR complex 1 (TORC1) controls cilia length via translation, impacting development and disease.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- The target-of-rapamycin (TOR) pathway is crucial for cellular growth, division, and metabolism.
- TOR pathway disruptions are linked to cilia abnormalities and ciliopathic diseases like renal cysts.
- The precise mechanism connecting TOR signaling to cilia length and function remained unclear.
Purpose of the Study:
- To elucidate how the TOR pathway influences cilia length and function.
- To investigate the role of TOR complex 1 (TORC1) in cilia regulation.
- To explore the impact of TOR signaling on embryonic development and ciliopathies.
Main Methods:
- Utilized zebrafish and Chlamydomonas as model systems.
- Employed genetic and molecular tools to manipulate the TOR pathway.
- Analyzed cilia morphology and function using advanced imaging and assays.
Main Results:
- Demonstrated TORC1-mediated control of cilia length through translational regulation of ciliary precursors.
- Showed that aberrant TORC1 signaling in zebrafish causes left-right asymmetric patterning defects.
- Identified impaired ciliary motility and fluid flow in the Kupffer's vesicle as a consequence of disrupted TORC1 signaling.
Conclusions:
- TORC1 signaling is a key regulator of cilia length via translational control.
- Dysfunctional TORC1 signaling contributes to developmental defects, including laterality patterning.
- A combined zebrafish and Chlamydomonas approach effectively dissects the TOR-cilium relationship.
