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

Abrar A. Aljiboury, Eric Ingram, Nikhila Krishnan, Favour Ononiwu, Debadrita Pal, Julie Manikas, Christopher Taveras, Nicole A. Hall, Jonah Da Silva, Judy Freshour, Heidi Hehnly

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

An essential process during Danio rerio's left-right organizer (Kupffer's Vesicle, KV) formation is the formation of a motile cilium by developing KV cells which extends into the KV lumen. Beating of motile cilia within the KV lumen directs fluid flow to establish the embryo's left-right axis. However, the timepoint at which KV cells start to form cilia and how cilia formation is coordinated with KV lumen formation have not been examined. We identified that nascent KV cells form cilia at their centrosomes at random intracellular positions that then move towards a forming apical membrane containing cystic fibrosis transmembrane conductance regulator (CFTR). Using optogenetic clustering approaches, we found that Rab35 positive membranes recruit Rab11 to modulate CFTR delivery to the apical membrane, which is required for lumen opening, and subsequent cilia extension into the lumen. Once the intracellular cilia reach the CFTR positive apical membrane, Arl13b-positive cilia extend and elongate in a Rab8 dependent manner into the forming lumen once the lumen reaches an area of 300 μm2. These studies demonstrate the need to acutely coordinate Rab8, Rab11, and Rab35-mediated membrane trafficking events to ensure appropriate timing in lumen and cilia formation during KV development.

Original languageEnglish (US)
Article numbere1010765
JournalPLoS genetics
Volume19
Issue number5 May
DOIs
StatePublished - May 15 2023

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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