FUZ

Cilia effects upon perturbation of FUZ

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-5.88) PMID:29459680
• Pusapati et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, neg_rank=378, lfc=-3.19) PMID:30270045

Phenotypes

Mouse phenotype:

abnormal placenta morphology, cleft palate, preweaning lethality, complete penetrance, abnormal tail morphology, abnormal heart looping, abnormal placenta vasculature, edema, abnormal blood vessel morphology, abnormal craniofacial morphology, anophthalmia, syndactyly, abnormal optic vesicle formation, abnormal limb morphology, hemorrhage, facial cleft, abnormal neural tube morphology

Mouse ciliopathy phenotype:

abnormal facial morphology, abnormal heart morphology, polydactyly, abnormal neural tube closure

Ciliopathy associations

• Joubert Syndrome
• Orofaciodigital Syndrome
• Short-Rib Thoracic Dysplasia

Subcellular localization

basal body, lysosomes

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Cell migration & adhesion
• Signaling (Hedgehog, GPCRs, ion channels)

Function

Critical regulator of cilia structure and function. Trafficking and localisation of retrograde, but not anterograde, intraflagellar transport proteins, governing their traffic from the cytoplasm to the basal body and then to the ciliary tip, representing a role in maintaining ciliary trafficking to the distal axoneme (22778277). FUZ is required for normal ciliogenesis, regulates trafficking and actin dynamics at basal body (via ARHGAP35). Fuz⁻/⁻ mutants have fewer and shorter cilia. (19767740) Biallelic FUZ LOF variants cause OFD syndrome with polydactyly, orofacial cleft, short ribs and cardiac defects. Part of CPLANE complex; involved in IFT vesicular trafficking within primary cilia (PMID:38702430).

Model organism evidence