ArticleDisease models & mechanisms2015
The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning and epithelial branching morphogenesis in mice via the non-canonical Wnt pathway.
Article in Disease models & mechanisms, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- Primary cilia: master conductors of cellular communication in development and disease.Nature reviews. Nephrology · 2026Review
- TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development.PLoS biology · 2026Article
- Genetic Characterization of Joubert Syndrome with COACH Features and in Silico Prediction ofMedical journal of the Islamic Republic of Iran · 2026Article
- Cleavage of the Meckel-Gruber syndrome protein TMEM67 by ADAMTS9 uncouples Wnt signaling and ciliogenesis.Nature communications · 2025Article
- A differential requirement for ciliary transition zone proteins in human and mouse neural progenitor fate specification.Nature communications · 2025Article
- Ventral body wall closure: Mechanistic insights from mouse models and translation to human pathology.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Review
- Neuronal guidance behaviours: the primary cilium perspective.Frontiers in cell and developmental biology · 2025Review
- Joubert syndrome-derived induced pluripotent stem cells show altered neuronal differentiation in vitro.Cell and tissue research · 2024Article
- Immunomodulatory potential of primary cilia in the skin.Frontiers in immunology · 2024Review
- Medullary Tegmental Cap Dysplasia: Fetal and Postnatal Presentations of a Unique Brainstem Malformation.AJNR. American journal of neuroradiology · 2023Review
- The Joubert-Meckel-Nephronophthisis Spectrum of Ciliopathies.Annual review of genomics and human genetics · 2022Review
- Interpreting ciliopathy-associated missense variants of uncertain significance (VUS) in Caenorhabditis elegans.Human molecular genetics · 2022Article
- Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity.Developmental cell · 2021Article
- Structure of the human Meckel-Gruber protein Meckelin.Science advances · 2021Article
- Genes causing congenital hydrocephalus: Their chromosomal characteristics of telomere proximity and DNA compositions.Experimental neurology · 2021Review
- Dysregulation of sonic hedgehog signaling causes hearing loss in ciliopathy mouse models.eLife · 2020Article
- Loss of ciliary transition zone protein TMEM107 leads to heterotaxy in mice.Developmental biology · 2020Article
- Placental defects lead to embryonic lethality in mice lacking the Formin and PCP proteins Daam1 and Daam2.PloS one · 2020Article
- Comparative genomics provides new insights into the remarkable adaptations of the African wild dog (Lycaon pictus).Scientific reports · 2019Article
- The ciliary Frizzled-like receptor Tmem67 regulates canonical Wnt/β-catenin signalling in the developing cerebellum via Hoxb5.Scientific reports · 2019Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
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Abstract
Ciliopathies are a group of developmental disorders that manifest with multi-organ anomalies. Mutations in TMEM67 (MKS3) cause a range of human ciliopathies, including Meckel-Gruber and Joubert syndromes. In this study we describe multi-organ developmental abnormalities in the Tmem67(tm1Dgen/H1) knockout mouse that closely resemble those seen in Wnt5a and Ror2 knockout mice. These include pulmonary hypoplasia, ventricular septal defects, shortening of the body longitudinal axis, limb abnormalities, and cochlear hair cell stereociliary bundle orientation and basal body/kinocilium positioning defects. The basal body/kinocilium complex was often uncoupled from the hair bundle, suggesting aberrant basal body migration, although planar cell polarity and apical planar asymmetry in the organ of Corti were normal. TMEM67 (meckelin) is essential for phosphorylation of the non-canonical Wnt receptor ROR2 (receptor-tyrosine-kinase-like orphan receptor 2) upon stimulation with Wnt5a-conditioned medium. ROR2 also colocalises and interacts with TMEM67 at the ciliary transition zone. Additionally, the extracellular N-terminal domain of TMEM67 preferentially binds to Wnt5a in an in vitro binding assay. Cultured lungs of Tmem67 mutant mice failed to respond to stimulation of epithelial branching morphogenesis by Wnt5a. Wnt5a also inhibited both the Shh and canonical Wnt/β-catenin signalling pathways in wild-type embryonic lung. Pulmonary hypoplasia phenotypes, including loss of correct epithelial branching morphogenesis and cell polarity, were rescued by stimulating the non-canonical Wnt pathway downstream of the Wnt5a-TMEM67-ROR2 axis by activating RhoA. We propose that TMEM67 is a receptor that has a main role in non-canonical Wnt signalling, mediated by Wnt5a and ROR2, and normally represses Shh signalling. Downstream therapeutic targeting of the Wnt5a-TMEM67-ROR2 axis might, therefore, reduce or prevent pulmonary hypoplasia in ciliopathies and other congenital conditions.
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