Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
PURPOSE: To identify the mutation and cell biological underpinnings of photoreceptor defects in zebrafish au5 mutants.
METHODS: Whole genome sequencing and SNP mapping were used to determine the genomic interval that harbors the au5 mutation. A candidate mutation was cloned and sequenced, and mRNA rescue used to validate that the affected gene was correctly identified. In situ hybridization, immunohistochemistry, and confocal imaging were used to determine the effects on photoreceptor development and maintenance in mutant retinae, and to determine if ciliogenesis or cilia-dependent development was affected in mutant embryos. Expression of tagged proteins and high-speed in vivo confocal imaging was used to quantify intraflagellar transport (IFT) and IFT particle localization within multiciliated cells of the Xenopus epidermis.
RESULTS: The au5 mutants possess a nonsense mutation in cluap1, which encodes a component of the IFT machinery. Photoreceptor defects result from degeneration of photoreceptors, and defects in ciliogenesis precede degeneration. Cilia in the olfactory pit are absent, and left-rightheart positioning is aberrant, consistent with a role for cluap1 during ciliogenesis and cilia-dependent development. High-speed in vivo imaging demonstrates that cluap1 undergoes IFT and that it moves along the cilium bidirectionally, with similar localization and kinetics as IFT20, an IFT-B complex component.
CONCLUSIONS: We identified a novel mutation in cluap1 and determined that photoreceptor maintenance is dependent on cluap1. Imaging data support a model in which cluap1 is a component of the IFT-B complex, and cilia formation requires cluap1 function. These data may provide new insights into the mechanism of photoreceptor degeneration in retinal ciliopathies.
Ashe,
Mutations in mouse Ift144 model the craniofacial, limb and rib defects in skeletal ciliopathies.
2012, Pubmed
Ashe,
Mutations in mouse Ift144 model the craniofacial, limb and rib defects in skeletal ciliopathies.
2012,
Pubmed Badano,
The ciliopathies: an emerging class of human genetic disorders.
2006,
Pubmed Baker,
Making sense of cilia in disease: the human ciliopathies.
2009,
Pubmed Baye,
The N-terminal region of centrosomal protein 290 (CEP290) restores vision in a zebrafish model of human blindness.
2011,
Pubmed Beales,
IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy.
2007,
Pubmed Boldt,
Disruption of intraflagellar protein transport in photoreceptor cilia causes Leber congenital amaurosis in humans and mice.
2011,
Pubmed Botilde,
Cluap1 localizes preferentially to the base and tip of cilia and is required for ciliogenesis in the mouse embryo.
2013,
Pubmed Brooks,
Control of vertebrate intraflagellar transport by the planar cell polarity effector Fuz.
2012,
Pubmed
,
Xenbase Brooks,
The Small GTPase Rsg1 is important for the cytoplasmic localization and axonemal dynamics of intraflagellar transport proteins.
2013,
Pubmed
,
Xenbase Chaya,
ICK is essential for cell type-specific ciliogenesis and the regulation of ciliary transport.
2014,
Pubmed Chung,
Coordinated genomic control of ciliogenesis and cell movement by RFX2.
2014,
Pubmed
,
Xenbase Duldulao,
Cilia localization is essential for in vivo functions of the Joubert syndrome protein Arl13b/Scorpion.
2009,
Pubmed Estrada-Cuzcano,
Non-syndromic retinal ciliopathies: translating gene discovery into therapy.
2012,
Pubmed Follit,
Characterization of mouse IFT complex B.
2009,
Pubmed Huangfu,
Cilia and Hedgehog responsiveness in the mouse.
2005,
Pubmed Hudak,
The intraflagellar transport protein ift80 is essential for photoreceptor survival in a zebrafish model of jeune asphyxiating thoracic dystrophy.
2010,
Pubmed Ishikawa,
Ciliogenesis: building the cell's antenna.
2011,
Pubmed Ishikura,
Identification of CLUAP1 as a human osteosarcoma tumor-associated antigen recognized by the humoral immune system.
2007,
Pubmed Jowett,
Whole-mount in situ hybridizations on zebrafish embryos using a mixture of digoxigenin- and fluorescein-labelled probes.
1994,
Pubmed Kimmel,
Stages of embryonic development of the zebrafish.
1995,
Pubmed
,
Xenbase Krock,
The intraflagellar transport protein IFT57 is required for cilia maintenance and regulates IFT-particle-kinesin-II dissociation in vertebrate photoreceptors.
2008,
Pubmed Lahiry,
A multiplex human syndrome implicates a key role for intestinal cell kinase in development of central nervous, skeletal, and endocrine systems.
2009,
Pubmed Lee,
An ENU mutagenesis screen in zebrafish for visual system mutants identifies a novel splice-acceptor site mutation in patched2 that results in Colobomas.
2012,
Pubmed Lehman,
The Oak Ridge Polycystic Kidney mouse: modeling ciliopathies of mice and men.
2008,
Pubmed Li,
Qilin is essential for cilia assembly and normal kidney development in zebrafish.
2011,
Pubmed Miller,
Cauli: a mouse strain with an Ift140 mutation that results in a skeletal ciliopathy modelling Jeune syndrome.
2013,
Pubmed Murayama,
The dyf-3 gene encodes a novel protein required for sensory cilium formation in Caenorhabditis elegans.
2005,
Pubmed Novarino,
Modeling human disease in humans: the ciliopathies.
2011,
Pubmed Obholzer,
Rapid positional cloning of zebrafish mutations by linkage and homozygosity mapping using whole-genome sequencing.
2012,
Pubmed Ou,
The PKD protein qilin undergoes intraflagellar transport.
2005,
Pubmed Pan,
Mechanism of transport of IFT particles in C. elegans cilia by the concerted action of kinesin-II and OSM-3 motors.
2006,
Pubmed Pasek,
Mammalian Clusterin associated protein 1 is an evolutionarily conserved protein required for ciliogenesis.
2012,
Pubmed Pazour,
The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance.
2002,
Pubmed Pretorius,
Functional analysis of BBS3 A89V that results in non-syndromic retinal degeneration.
2011,
Pubmed Qin,
Intraflagellar transport protein 122 antagonizes Sonic Hedgehog signaling and controls ciliary localization of pathway components.
2011,
Pubmed Rachel,
Photoreceptor sensory cilia and ciliopathies: focus on CEP290, RPGR and their interacting proteins.
2012,
Pubmed Raymond,
Developmental patterning of rod and cone photoreceptors in embryonic zebrafish.
1995,
Pubmed Sayer,
The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4.
2006,
Pubmed Schou,
A divergent calponin homology (NN-CH) domain defines a novel family: implications for evolution of ciliary IFT complex B proteins.
2014,
Pubmed Snow,
Two anterograde intraflagellar transport motors cooperate to build sensory cilia on C. elegans neurons.
2004,
Pubmed Sukumaran,
Early defects in photoreceptor outer segment morphogenesis in zebrafish ift57, ift88 and ift172 Intraflagellar Transport mutants.
2009,
Pubmed Sun,
A genetic screen in zebrafish identifies cilia genes as a principal cause of cystic kidney.
2004,
Pubmed
,
Xenbase Takahashi,
Isolation and characterization of a novel gene CLUAP1 whose expression is frequently upregulated in colon cancer.
2004,
Pubmed Texier,
Elution profile analysis of SDS-induced subcomplexes by quantitative mass spectrometry.
2014,
Pubmed Tran,
THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia.
2008,
Pubmed Tsujikawa,
Intraflagellar transport genes are essential for differentiation and survival of vertebrate sensory neurons.
2004,
Pubmed Uribe,
Immunohistochemistry on cryosections from embryonic and adult zebrafish eyes.
2007,
Pubmed Werner,
Understanding ciliated epithelia: the power of Xenopus.
2012,
Pubmed
,
Xenbase Wheway,
The role of primary cilia in the development and disease of the retina.
2014,
Pubmed Wright,
Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait.
2010,
Pubmed Yelon,
Restricted expression of cardiac myosin genes reveals regulated aspects of heart tube assembly in zebrafish.
1999,
Pubmed
