PUBLICATION

Daw1 regulates the timely onset of cilia motility during development

Authors
Bearce, E.A., Irons, Z.H., Craig, S.B., Kuhns, C.J., Sabazali, C., Farnsworth, D.R., Miller, A.C., Grimes, D.T.
ID
ZDB-PUB-220622-4
Date
2022
Source
Development (Cambridge, England)   149(12): (Journal)
Registered Authors
Farnsworth, Dylan, Grimes, Daniel T., Miller, Adam
Keywords
Axis development, Daw1, Motile cilia, Primary ciliary dyskinesia, Scoliosis, Zebrafish
MeSH Terms
  • Animals
  • Cell Movement
  • Cilia*/metabolism
  • Dyneins*/metabolism
  • Humans
  • Mutation/genetics
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
35708608 Full text @ Development
Abstract
Motile cilia generate cell propulsion and extracellular fluid flows that are crucial for airway clearance, fertility and left-right patterning. Motility is powered by dynein arm complexes that are assembled in the cytoplasm then imported into the cilium. Studies in Chlamydomonas reinhardtii showed that ODA16 is a cofactor which promotes dynein arm import. Here, we demonstrate that the zebrafish homolog of ODA16, Daw1, facilitates the onset of robust cilia motility during development. Without Daw1, cilia showed markedly reduced motility during early development; however, motility subsequently increased to attain close to wild-type levels. Delayed motility onset led to differential effects on early and late cilia-dependent processes. Remarkably, abnormal body axis curves, which formed during the first day of development due to reduced cilia motility, self-corrected when motility later reached wild-type levels. Zebrafish larva therefore possess the ability to survey and correct body shape abnormalities. This work defines Daw1 as a factor which promotes the onset of timely cilia motility and can explain why human patients harboring DAW1 mutations exhibit significant laterality perturbations but mild airway and fertility complications.
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
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Mapping