The LIM protein Ajuba is required for ciliogenesis and left-right axis determination in medaka.
Cilia are microtubule-based organelles that are present on the surfaces of almost all vertebrate cells. Most cilia function as sensory or molecular transport structures. Malfunctions of cilia have been implicated in several diseases of human development. The assembly of cilia is initiated by the centriole (or basal body), and several centrosomal proteins are involved in this process. The mammalian LIM protein Ajuba is a well-studied centrosomal protein that regulates cell division but its role in ciliogenesis is unknown. In this study, we isolated the medaka homolog of Ajuba and showed that Ajuba localizes to basal bodies of cilia in growth-arrested cells. Knockdown of Ajuba resulted in randomized left-right organ asymmetries and altered expression of early genes responsible for left-right body axis determination. At the cellular level, we found that Ajuba function was essential for ciliogenesis in the cells lining Kupffer's vesicle; it is these cells that induce the asymmetric fluid flow required for left-right axis determination. Taken together, our findings identify a novel role for Ajuba in the regulation of vertebrate ciliogenesis and left-right axis determination.
Nagai
Yoko
Y
Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Asaoka
Yoichi
Y
Namae
Misako
M
Saito
Kota
K
Momose
Haruka
H
Mitani
Hiroshi
H
Furutani-Seiki
Makoto
M
Katada
Toshiaki
T
Nishina
Hiroshi
H
D000818:Animals; D002923:Cilia / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D003001:Cloning, Molecular; D055785:Gene Knockdown Techniques; D006321:Heart / Q000196:embryology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000002:abnormalities; D008870:Microtubules / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009990:Oryzias / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000002:abnormalities
D018398:Homeodomain Proteins