UM  > 健康科學學院
Dstyk mutation leads to congenital scoliosis-like vertebral malformations in zebrafish via dysregulated mTORC1/TFEB pathway
Sun,Xianding1; Zhou,Yang2; Zhang,Ruobin1; Wang,Zuqiang1; Xu,Meng1; Zhang,Dali1; Huang,Junlan1; Luo,Fengtao1; Li,Fangfang1; Ni,Zhenhong1; Zhou,Siru1; Chen,Hangang1; Chen,Shuai1; Chen,Liang1; Du,Xiaolan1; Chen,Bo1; Huang,Haiyang1; Liu,Peng1; Yin,Liangjun3; Qiu,Juhui4; Chen,Di5; Deng,Chuxia6,7; Xie,Yangli1; Luo,Lingfei2; Chen,Lin1
2020-12-01
Source PublicationNature Communications
Volume11Issue:1
AbstractCongenital scoliosis (CS) is a complex genetic disorder characterized by vertebral malformations. The precise etiology of CS is not fully defined. Here, we identify that mutation in dual serine/threonine and tyrosine protein kinase (dstyk) lead to CS-like vertebral malformations in zebrafish. We demonstrate that the scoliosis in dstyk mutants is related to the wavy and malformed notochord sheath formation and abnormal axial skeleton segmentation due to dysregulated biogenesis of notochord vacuoles and notochord function. Further studies show that DSTYK is located in late endosomal/lysosomal compartments and is involved in the lysosome biogenesis in mammalian cells. Dstyk knockdown inhibits notochord vacuole and lysosome biogenesis through mTORC1-dependent repression of TFEB nuclear translocation. Inhibition of mTORC1 activity can rescue the defect in notochord vacuole biogenesis and scoliosis in dstyk mutants. Together, our findings reveal a key role of DSTYK in notochord vacuole biogenesis, notochord morphogenesis and spine development through mTORC1/TFEB pathway.
DOI10.1038/s41467-019-14169-z
URLView the original
Language英语
Fulltext Access
Citation statistics
Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorXie,Yangli
Affiliation1.Department of Wound Repair and Rehabilitation,State Key Laboratory of Trauma,Burns and Combined Injury,Trauma Center,Research Institute of Surgery,Daping Hospital,Army Medical University,Chongqing,400042,China
2.Key Laboratory of Freshwater Fish Reproduction and Development,Ministry of Education,Laboratory of Molecular Developmental Biology,School of Life Sciences,Southwest University,Beibei,400715,China
3.Department of Orthopedic Surgery,The Second Affiliated Hospital,Chongqing Medical University,Chongqing,400010,China
4.College of Bioengineering,Chongqing University,Chongqing,400044,China
5.Department of Orthopedic Surgery,Rush University Medical Center,Chicago,60612,United States
6.Genetics of Development and Disease Branch,National Institute of Diabetes,Digestive and Kidney Diseases,National Institutes of Health,Bethesda,20892,United States
7.Faculty of Health Sciences,University of Macau,Macao
Recommended Citation
GB/T 7714
Sun,Xianding,Zhou,Yang,Zhang,Ruobin,et al. Dstyk mutation leads to congenital scoliosis-like vertebral malformations in zebrafish via dysregulated mTORC1/TFEB pathway[J]. Nature Communications,2020,11(1).
APA Sun,Xianding.,Zhou,Yang.,Zhang,Ruobin.,Wang,Zuqiang.,Xu,Meng.,...&Chen,Lin.(2020).Dstyk mutation leads to congenital scoliosis-like vertebral malformations in zebrafish via dysregulated mTORC1/TFEB pathway.Nature Communications,11(1).
MLA Sun,Xianding,et al."Dstyk mutation leads to congenital scoliosis-like vertebral malformations in zebrafish via dysregulated mTORC1/TFEB pathway".Nature Communications 11.1(2020).
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Sun,Xianding]'s Articles
[Zhou,Yang]'s Articles
[Zhang,Ruobin]'s Articles
Baidu academic
Similar articles in Baidu academic
[Sun,Xianding]'s Articles
[Zhou,Yang]'s Articles
[Zhang,Ruobin]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Sun,Xianding]'s Articles
[Zhou,Yang]'s Articles
[Zhang,Ruobin]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.