Dissecting the functional interplay between the TOR pathway and the cilium in zebrafish

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.