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)
| Autor: | Takahiko Yokoyama, Masato Kinoshita, Takashi Nakakura, Toshiyuki Nishimaki, Satoshi Ansai, Daisuke Kobayashi, Motoyuki Ogawa, Anshin Asano-Hoshino, Haruo Hagiwara |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Axoneme Embryo Nonmammalian Movement Oryzias Motility Biology Flagellum Morpholinos 03 medical and health sciences 0302 clinical medicine Intraflagellar transport Internal medicine medicine Animals Amino Acid Sequence Cilia RNA Messenger Molecular Biology Primary ciliary dyskinesia Body Patterning Zinc finger Gene knockdown Polycystic Kidney Diseases Base Sequence Cilium Tumor Suppressor Proteins Dyneins Gene Expression Regulation Developmental Epistasis Genetic Zinc Fingers Cell Biology medicine.disease Spermatozoa Cell biology 030104 developmental biology Endocrinology Phenotype Scoliosis Motile cilium 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Developmental biology. 430(1) |
| ISSN: | 1095-564X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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