RRC ID 50576
Author Kobayashi D, Asano-Hoshino A, Nakakura T, Nishimaki T, Ansai S, Kinoshita M, Ogawa M, Hagiwara H, Yokoyama T.
Title 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).
Journal 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.
Volume 430(1)
Pages 69-79
Published 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
Times Cited 6
Medaka Hatching enzyme d-rR/TOKYO (MT837) zmynd10 (MT1419)