ArticleNature genetics2008
THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia.
Article in Nature genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 221 papers.
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Who cites it
221 citing papers in PubMed, 342 citations in OpenAlex.
- Article
- Ttc21b is required for proper proliferation of neural progenitor cells.Disease models & mechanisms · 2026Article
- The role of the primary cilium in thyroid function and dysfunction with implications for thyroid disease.Histochemistry and cell biology · 2025Review
- Genetic interaction ofbioRxiv : the preprint server for biology · 2025Article
- IFT139 regulates Hedgehog signaling and cilia structure through ciliary protein localization.Biology open · 2025Article
- Inhibition of Hedgehog signaling does not mitigate polycystic kidney disease severity in a Pkd1 mutant mouse model.Journal of cell science · 2025Article
- Elucidating Mechanisms of Hypomorphic WDR19-Related Kidney Failure.Kidney international reports · 2025Article
- TAOK2 drives opposing cilia length deficits in 16p11.2 deletion and duplication carriers.Stem cell reports · 2025Article
- Cilia at the crossroad: convergence of regulatory mechanisms to govern cilia dynamics during cell signaling and the cell cycle.Cell & bioscience · 2025Review
- C21ORF2 mutations point towards primary cilia dysfunction in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2025Article
- A defined tubby domain β-barrel surface region of TULP3 mediates ciliary trafficking of diverse cargoes.Molecular biology of the cell · 2025Article
- SMPD4-mediated sphingolipid metabolism regulates brain and primary cilia development.Development (Cambridge, England) · 2024Article
- Intraflagellar transport: A critical player in photoreceptor development and the pathogenesis of retinal degenerative diseases.Cytoskeleton (Hoboken, N.J.) · 2024Review
- IFT88 maintains sensory function by localising signalling proteins alongLife science alliance · 2024Article
- Primary cilia are critical for tracheoesophageal septation.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Article
- Label-free proteomic comparison reveals ciliary and nonciliary phenotypes of IFT-A mutants.Molecular biology of the cell · 2024Article
- The exocyst complex and intracellular vesicles mediate soluble protein trafficking to the primary cilium.Communications biology · 2024Article
- Uncovering cilia function in glial development.Annals of human genetics · 2024Review
- Autonomous and non-cell autonomous role of cilia in structural birth defects in mice.PLoS biology · 2023Article
- Development of an In Vitro Model for Inflammation Mediated Renal Toxicity Using 3D Renal Tubules and Co-Cultured Human Immune Cells.Tissue engineering and regenerative medicine · 2023Article
161 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Characterization of previously described intraflagellar transport (IFT) mouse mutants has led to the proposition that normal primary cilia are required for mammalian cells to respond to the sonic hedgehog (SHH) signal. Here we describe an N-ethyl-N-nitrosourea-induced mutant mouse, alien (aln), which has abnormal primary cilia and shows overactivation of the SHH pathway. The aln locus encodes a novel protein, THM1 (tetratricopeptide repeat-containing hedgehog modulator-1), which localizes to cilia. aln-mutant cilia have bulb-like structures at their tips in which IFT proteins (such as IFT88) are sequestered, characteristic of Chlamydomonas reinhardtii and Caenorhabditis elegans retrograde IFT mutants. RNA-interference knockdown of Ttc21b (which we call Thm1 and which encodes THM1) in mouse inner medullary collecting duct cells expressing an IFT88-enhanced yellow fluorescent protein fusion recapitulated the aln-mutant cilial phenotype, and live imaging of these cells revealed impaired retrograde IFT. In contrast to previously described IFT mutants, Smoothened and full-length glioblastoma (GLI) proteins localize to aln-mutant cilia. We hypothesize that the aln retrograde IFT defect causes sequestration of IFT proteins in aln-mutant cilia and leads to the overactivated SHH signaling phenotype. Specifically, the aln mutation uncouples the roles of anterograde and retrograde transport in SHH signaling, suggesting that anterograde IFT is required for GLI activation and that retrograde IFT modulates this event.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.