IFT46 plays an essential role in cilia development.
Cilia are microtubule-based structures that project into the extracellular space. Ciliary defects are associated with several human diseases, including polycystic kidney disease, primary ciliary dyskinesia, left-right axis patterning, hydrocephalus and retinal degeneration. However, the genetic and cellular biological control of ciliogenesis remains poorly understood. The IFT46 is one of the highly conserved intraflagellar transport complex B proteins. In zebrafish, ift46 is expressed in various ciliated tissues such as Kupffer׳s vesicle, pronephric ducts, ears and spinal cord. We show that ift46 is localized to the basal body. Knockdown of ift46 gene results in multiple phenotypes associated with various ciliopathies including kidney cysts, pericardial edema and ventral axis curvature. In ift46 morphants, cilia in kidney and spinal canal are shortened and abnormal. Similar ciliary defects are observed in otic vesicles, lateral line hair cells, olfactory pits, but not in Kupffer׳s vesicle. To explore the functions of Ift46 during mouse development, we have generated Ift46 knock-out mice. The Ift46 mutants have developmental defects in brain, neural tube and heart. In particular Ift46(-/-) homozygotes displays randomization of the embryo heart looping, which is a hallmark of defective left-right (L/R) axis patterning. Taken together, our results demonstrated that IFT46 has an essential role in vertebrate ciliary development.
Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.
Mi-Sun
MS
Lee
Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.
Kyu-Seok
KS
Hwang
Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
Hyun-Woo
HW
Oh
Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
Kim
K
Ji-Ae
Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.
Hyun-Taek
HT
Kim
Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
Hyun-Soo
HS
Cho
Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
Jeong-Ju
JJ
Lee
Department of Biological Science, Sookmyung Women׳s University, Seoul 140-742, Republic of Korea.
Je
J
Yeong Ko
Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.
Jung-Hwa
JH
Choi
Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.
Yun-Mi
YM
Jeong
Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.
Kwan-Hee
KH
You
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
Joon
J
Kim
Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
Doo-Sang
DS
Park
Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
Ki-Hoan
KH
Nam
Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology (CDB), Kobe 650-0047, Japan.
Shinichi
S
Aizawa
Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology (CDB), Kobe 650-0047, Japan.
Hiroshi
H
Kiyonari
Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology (CDB), Kobe 650-0047, Japan.
Go
G
Shioi
Department of Biological Science, Sookmyung Women׳s University, Seoul 140-742, Republic of Korea.
Jong-Hoon
JH
Park
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109-5646, USA. Electronic address: weibinz@med.umich.edu.
Weibin
W
Zhou
Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea. Electronic address: nskim37@kribb.re.kr.
Nam-Soon
NS
Kim
Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: zebrakim@cnu.ac.kr.
Cheol-Hee
CH
Kim
D000595:Amino Acid Sequence; D000818:Animals; D064652:Basal Bodies / Q000378:metabolism; D002923:Cilia / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D003598:Cytoskeletal Proteins; C519209:IFT46 protein, mouse; C000598108:IFT46 protein, zebrafish; D047908:Intracellular Signaling Peptides and Proteins; D029961:Zebrafish Proteins
Cilia; Ciliopathy; IFT; IFT46; Intraflagellar transport; KO mouse; L/R defect; Zebrafish