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Abstract: SA-PO546

Silencing of cep104 in Zebrafish Embryos Gives Rise to a Ciliopathy Phenotype

Session Information

  • Developmental Biology
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Developmental Biology and Inherited Kidney Diseases

  • 401 Developmental Biology


  • Molinari, Elisa, University of Newcastle, Newcastle upon Tyne, United Kingdom
  • Ramsbottom, Simon, University of Newcastle, Newcastle upon Tyne, United Kingdom
  • Sayer, John, University of Newcastle, Newcastle upon Tyne, United Kingdom

Joubert syndrome (JBTS) is a rare autosomal recessive ciliopathy characterized by a cerebellar hypoplasia which may be accompanied by additional symptoms including developmental delay, ataxia, intellectual disabilities, retinal dystrophy and juvenile cystic renal disease (nephronophthisis, NPHP). To date, JBTS-causing mutations have been identified in 28 genes (JBTS1-JBTS28). JBTS25 is associated with the CEP104 gene. Of note, the cilia phenotype of CEP104 mutation carriers has not yet been reported nor has genetic silencing been tested in vertebrate models. Our results demonstrate for the first time in vivo a function for cep104 in zebrafish development.


Using antisense morpholino oligonucleotide (MO) technology, we silenced cep104 in Danio rerio (zebrafish). To assess specific phenotypes, we used wild type zebrafish golden and AB strains, alongside the transgenic islet-1:GFP strain which expresses GFP in cranial motor neurons under the control of islet1 promoter and the cmlc2:GFP transgenic strain, expressing the GFP gene under the control of the cmcl2 promoter.


cep104 MO-injected zebrafish embryos at 48 hpf displayed cardiac phenotypes, tail curvature and microophthalmia, which can be rescued by co-injection of a human CEP104 mRNA, confirming the specificity of the MO. Analysis of Kupffer’s vesicle, a ciliated organelle important for left-right axis formation, showed a ciliary defect, with a reduction in ciliary length. Morphant embryos display situs inversus, with reversed cardiac looping. Most relevant in respect to JBTS, characteristic developmental defects were observed within the brains of cep104 zebrafish morphants, with a major involvement of oculomotor neurons. These specific defects were also rescued by co-administration of CEP104 mRNA.


These data reveal that cep104 morphant phenotypes are highly consistent with a ciliopathy syndrome, and suggest a role for cep104 in cilia formation within Kupffer’s vesicle as well as development of the heart and cranial nerves.


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