{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nFuz is a planar cell polarity effector that plays a crucial role during early embryogenesis. It controls the formation of primary cilia by localizing to the basal body and ciliary axoneme and orchestrating the delivery of key trafficking proteins such as Rab8. Disruption of Fuz function compromises neural tube formation, leading to neural tube defects as observed in both mouse models and human patients. In these models, loss‐of‐function mutations in Fuz disrupt ciliary assembly and impair directional cell movements, thereby perturbing the planar cell polarity pathway essential for proper neural patterning and morphogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in neural development, Fuz is essential for integrating multiple signaling pathways that orchestrate craniofacial and skeletal patterning. Fuz mutations have been linked to aberrant Hedgehog (Hh) activity and dysfunctional proteolytic processing of Gli transcription factors, which in turn affect vital processes such as hair follicle formation, palate morphogenesis, and skull bone patterning. In mutant models, loss of Fuz leads to dysregulation of both Hedgehog and canonical Wnt signaling, resulting in craniofacial anomalies such as high arched palate and craniosynostosis, and disrupting the balance between neural crest-derived and mesodermally-derived bone formation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFuz further modulates developmental signaling through interactions with key regulatory proteins. It influences the subcellular localization of core PCP components like Dishevelled and interacts biochemically with the G protein–coupled receptor Gpr161 to regulate its ciliary targeting, a process that is critical for fine-tuning Sonic hedgehog (Shh) pathway activity during neural tube development. Moreover, Fuz is indispensable for pituitary gland formation, where its loss leads to diminished Shh signaling and impaired expression of essential transcription factors, underscoring its broader impact on organogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Westley Heydeck, Huiqing Zeng, Aimin Liu "}, {"type": "b", "children": [{"type": "t", "text": "Planar cell polarity effector gene Fuzzy regulates cilia formation and Hedgehog signal transduction in mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dvdy.22130"}], "href": "https://doi.org/10.1002/dvdy.22130"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19877275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19877275"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Westley Heydeck, Aimin Liu "}, {"type": "b", "children": [{"type": "t", "text": "PCP effector proteins inturned and fuzzy play nonredundant roles in the patterning but not convergent extension of mammalian neural tube."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dvdy.22696"}], "href": "https://doi.org/10.1002/dvdy.22696"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21761479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21761479"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jung Hwa Seo, Yulia Zilber, Sima Babayeva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the planar cell polarity gene, Fuzzy, are associated with neural tube defects in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddr359"}], "href": "https://doi.org/10.1093/hmg/ddr359"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21840926"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21840926"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yulia Zilber, Sima Babayeva, Jung Hwa Seo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PCP effector Fuzzy controls cilial assembly and signaling by recruiting Rab8 and Dishevelled to the primary cilium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E12-06-0437"}], "href": "https://doi.org/10.1091/mbc.E12-06-0437"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23303251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23303251"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Daisy Dai, Huiping Zhu, Bogdan Wlodarczyk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fuz controls the morphogenesis and differentiation of hair follicles through the formation of primary cilia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2010.306"}], "href": "https://doi.org/10.1038/jid.2010.306"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20962855"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20962855"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zichao Zhang, Bogdan J Wlodarczyk, Karen Niederreither, et al. 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