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@ARTICLE{Epting:304581,
author = {D. Epting and J. Devane and R. Mertes and S. Kayser and M.
Helmstädter and P. Metzger and M. Börries$^*$ and C.
Bergmann and E. Ott},
title = {{T}ulp3 deficiency results in ciliopathy phenotypes during
zebrafish embryogenesis.},
journal = {Scientific reports},
volume = {15},
number = {1},
issn = {2045-2322},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-01904},
pages = {32435},
year = {2025},
abstract = {Ciliopathies, caused by defective cilia biogenesis or
function, comprise a genetically and clinically diverse
group of diseases. Primary cilia play pivotal roles in the
regulation of a multitude of signalling pathways during
development and tissue homeostasis. Cilia assembly,
maintenance and signalling depend on intraflagellar
transport (IFT). Tubby-like protein 3 (TULP3) functions as
an adapter protein for the ciliary trafficking of diverse
membrane cargos via an interaction with the IFT-A complex.
Recently, we and others have shown that individuals carrying
pathogenic TULP3 variants suffer from progressive liver,
kidney and heart disease. In line with these findings, adult
Tulp3 knockout zebrafish displayed liver fibrosis and kidney
cyst phenotypes. In the present study, we analysed the
functional consequences of Tulp3 deficiency during zebrafish
embryogenesis. Tulp3 deficiency resulted in well-known
ciliopathy-associated phenotypes including pronephric cysts,
body curvature and altered left-right asymmetry. Our
analysis of urotensin 2-related peptide (Urp) signalling,
which is required for proper spine morphogenesis, revealed
reduced expression of urp1 in Tulp3 knockout embryos. We
also observed scoliosis in a significant number of adult
Tulp3 knockout zebrafish. Analysis of ciliogenesis revealed
a reduced cilia number and ciliary length in Tulp3 deficient
embryos. In addition, Tulp3 deficiency resulted in
upregulation of cilia-dependent profibrotic Wnt and Jak/Stat
signalling components. Furthermore, we demonstrate that loss
of Tulp3 causes upregulation of genes related to liver
fibrosis. In conclusion, our data highlights a role of Tulp3
in proper cilia formation and function to maintain healthy
tissue architecture during zebrafish embryogenesis, and
provides further insight into the spectrum of cilia-related
phenotypes in adult zebrafish depleted for Tulp3 functions.},
cin = {FR01},
ddc = {600},
cid = {I:(DE-He78)FR01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40940409},
pmc = {pmc:PMC12432116},
doi = {10.1038/s41598-025-16584-3},
url = {https://inrepo02.dkfz.de/record/304581},
}