Daw1 regulates the timely onset of cilia motility during 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.

Urotensin II-Related Peptides, Urp1 and Urp2, Control Zebrafish Spine Morphology

“…1Ei). By contrast, we observed CTD in both cfap298 tm304 mutants that lack cilia motility in the central canal (Bearce et al, 2022) and sspo b1446 mutants in which the of 2 15 RF constituent SCOspondin is mutated, as expected (Fig. 1Ei and S2A-B).…”

“…By contrast, cfap298 tm304 mutants raised at restrictive temperatures, which exhibited reduced central canal cilia motility and CTD (Fig. 1E; Bearce et al, 2022), lacked RF. Instead, Sspo was diffusely localized in the central canal in these mutants (Fig.…”

“…Zebrafish larvae at 28-30 hpf were imaged using a Leica S9i stereomicroscope with integrated 10-magapixel camera. Body angles were calculated using ImageJ (Schindelin et al, 2012) as described in Bearce et al, 2022.…”

“…Zebrafi sh larvae at 28-30 hpf were imaged using a Leica S9i stereomicroscope with integrated 10-magapixel camera. Body angles were calculated using ImageJ (Schindelin et al, 2012) as described in Bearce et al, 2022. Quantitative reverse transcriptase PCR (qRT-PCR). RNA was extracted using a Zymo Direct-Zol RNA Miniprep kit (Zymo Research, R2051).…”

“…X-ray microcomputed tomography (µCT). Scans were performed using a vivaCT80 (Scanco Medical) at 18.5 µm voxel resolution as previously described (Bearce et al, 2022).…”