Dynein axonemal intermediate chain 2 is required for formation of the left-right body axis and kidney in medaka.
Ciliary defects lead to various diseases, such as primary ciliary dyskinesia (PCD) and polycystic kidney disease (PKD). We isolated a medaka mutant mii, which exhibits defects in the left-right (LR) polarity of organs, and found that mii encodes dynein axonemal intermediate chain 2a (dnai2a). Ortholog mutations were recently reported to cause PCD in humans. mii mutant embryos exhibited loss of nodal flow in Kupffer's Vesicle (KV), which is equivalent to the mammalian node, and abnormal expression of the left-specific gene. KV cilia in the mii mutant were defective in their outer dynein arms (ODAs), indicating that Dnai2a is required for ODA formation in KV cilia. While the mii mutant retained motility of the renal cilia and failed to show PKD, the loss of dnai2a and another dnai2 ortholog dnai2b led to PKD. These findings demonstrate that Dnai2 proteins control LR polarity and kidney formation through regulation of ciliary motility.
Nagao
Yusuke
Y
Department of Biological Sciences, Graduate School of Science, Nagoya University, Nagoya, Japan.
Cheng
Jinglei
J
Kamura
Keiichiro
K
Seki
Ryoko
R
Maeda
Aya
A
Nihei
Daichi
D
Koshida
Sumito
S
Wakamatsu
Yuko
Y
Fujimoto
Toyoshi
T
Hibi
Masahiko
M
Hashimoto
Hisashi
H
D000818:Animals; D056444:Axonemal Dyneins / Q000378:metabolism*; D001483:Base Sequence; D019521:Body Patterning; D002923:Cilia / Q000378:metabolism / Q000473:pathology; D004625:Embryo, Nonmammalian / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity; D009990:Oryzias / Q000196:embryology* / Q000235:genetics; D010641:Phenotype; D007690:Polycystic Kidney Diseases / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D012333:RNA, Messenger; D056444:Axonemal Dyneins