Rab8, Rab11, and Rab35 coordinate lumen and cilia formation during zebrafish left-right organizer development

Area of Science:

• Developmental Biology
• Cell Biology
• Genetics

Background:

• Kupffer's Vesicle (KV) in zebrafish is crucial for left-right axis determination.
• Motile cilia in KV direct embryonic fluid flow, but their formation timing and coordination with lumenogenesis are unclear.

Purpose of the Study:

• To investigate the temporal coordination between cilia formation and lumen development in zebrafish KV.
• To elucidate the molecular mechanisms governing cilia extension into the KV lumen.

Main Methods:

• Utilized optogenetic clustering approaches in zebrafish embryos.
• Investigated the roles of Rab GTPases (Rab8, Rab11, Rab35) and CFTR in KV development.

Main Results:

• Cilia initially form at random intracellular positions and migrate to the apical membrane.
• Rab35 and Rab11 mediate CFTR delivery, essential for lumen opening and cilia entry.
• Cilia extend into the lumen in a Rab8-dependent manner once the lumen reaches a critical size.

Conclusions:

• Coordinated membrane trafficking via Rab8, Rab11, and Rab35 is critical for precise timing of KV lumen and cilia formation.
• This study reveals a novel mechanism linking membrane trafficking to ciliogenesis during KV development.