RRC ID |
50576
|
著者 |
Kobayashi D, Asano-Hoshino A, Nakakura T, Nishimaki T, Ansai S, Kinoshita M, Ogawa M, Hagiwara H, Yokoyama T.
|
タイトル |
Loss of zinc finger MYND-type containing 10 (zmynd10) affects cilia integrity and axonemal localization of dynein arms, resulting in ciliary dysmotility, polycystic kidney and scoliosis in medaka (Oryzias latipes).
|
ジャーナル |
Dev Biol
|
Abstract |
Cilia and flagella are hair-like organelles that project from the cell surface and play important roles in motility and sensory perception. Motility defects in cilia and flagella lead to primary ciliary dyskinesia (PCD), a rare human disease. Recently zinc finger MYND-type containing 10 (ZMYND10) was identified in humans as a PCD-associated gene. In this study, we use medaka fish as a model to characterize the precise functions of zmynd10. In medaka, zmynd10 is exclusively expressed in cells with motile cilia. Embryos with zmynd10 Morpholino knockdown exhibited a left-right (LR) defect associated with loss of motility in Kupffer's vesicle (KV) cilia. This immotility was caused by loss of the outer dynein arms, which is a characteristic ultrastructural phenotype in PCD. In addition, KV cilia in zmynd10 knockdown embryos had a swollen and wavy morphology. Together, these results suggest that zmynd10 is a multi-functional protein that has independent roles in axonemal localization of dynein arms and in formation and/or maintenance of cilia. The C-terminal region of zmynd10 has a MYND-type zinc finger domain (zf-MYND) that is important for its function. Our rescue experiment showed that the zmynd10-ΔC truncated protein, which lacks zf-MYND, was still partially functional, suggesting that zmynd10 has another functional domain besides zf-MYND. To analyze the later stages of development, we generated a zmynd10 knockout mutant using transcription activator-like effector nuclease (TALEN) technology. Adult mutants exhibited sperm dysmotility, scoliosis and progressive polycystic kidney.
|
巻・号 |
430(1)
|
ページ |
69-79
|
公開日 |
2017-10-1
|
DOI |
10.1016/j.ydbio.2017.08.016
|
PII |
S0012-1606(17)30202-6
|
PMID |
28823919
|
MeSH |
Amino Acid Sequence
Animals
Axoneme / drug effects
Axoneme / metabolism*
Base Sequence
Body Patterning / drug effects
Body Patterning / genetics
Cilia / drug effects
Cilia / metabolism*
Dyneins / metabolism*
Embryo, Nonmammalian / drug effects
Embryo, Nonmammalian / metabolism
Epistasis, Genetic / drug effects
Gene Expression Regulation, Developmental / drug effects
Male
Morpholinos / pharmacology
Movement
Oryzias / embryology
Oryzias / genetics
Oryzias / metabolism*
Phenotype
Polycystic Kidney Diseases / metabolism*
Polycystic Kidney Diseases / pathology
RNA, Messenger / genetics
RNA, Messenger / metabolism
Scoliosis / metabolism*
Scoliosis / pathology
Spermatozoa / metabolism
Tumor Suppressor Proteins / chemistry
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / metabolism
Zinc Fingers
|
IF |
2.896
|
引用数 |
6
|
リソース情報 |
メダカ |
Hatching enzyme
d-rR/TOKYO (MT837)
zmynd10 (MT1419) |