IHB OpenIR  > 其他  > 期刊论文
Deficiency of lrp4 in zebrafish and human LRP4 mutation induce aberrant activation of Jagged-Notch signaling in fin and limb development
Tian, Jing1,6; Shao, Jinhui1; Liu, Cong1; Hou, Hsin-Yu2; Chou, Chih-Wei2; Shboul, Mohammad3; Li, Guo-Qing1; El-Khateeb, Mohammad4; Samarah, Omar Q.5; Kou, Yao1; Chen, Yu-Hsuan2; Chen, Mei-Jen2; Lyu, Zhaojie1; Chen, Wei-Leng2; Chen, Yu-Fu2; Sun, Yong-Hua6; Liu, Yi-Wen2
Corresponding AuthorTian, Jing(tianjing@nwu.edu.cn) ; Liu, Yi-Wen(dlslys@thu.edu.tw)
2019
Source PublicationCELLULAR AND MOLECULAR LIFE SCIENCES
ISSN1420-682X
Volume76Issue:1Pages:163-178
AbstractLow-density lipoprotein receptor-related protein 4 (LRP4) is a multi-functional protein implicated in bone, kidney and neurological diseases including Cenani-Lenz syndactyly (CLS), sclerosteosis, osteoporosis, congenital myasthenic syndrome and myasthenia gravis. Why different LRP4 mutation alleles cause distinct and even contrasting disease phenotypes remain unclear. Herein, we utilized the zebrafish model to search for pathways affected by a deficiency of LRP4. The lrp4 knockdown in zebrafish embryos exhibits cyst formations at fin structures and the caudal vein plexus, malformed pectoral fins, defective bone formation and compromised kidney morphogenesis; which partially phenocopied the human LRP4 mutations and were reminiscent of phenotypes resulting form a perturbed Notch signaling pathway. We discovered that the Lrp4-deficient zebrafish manifested increased Notch outputs in addition to enhanced Wnt signaling, with the expression of Notch ligand jagged1b being significantly elevated at the fin structures. To examine conservatism of signaling mechanisms, the effect of LRP4 missense mutations and siRNA knockdowns, including a novel missense mutation c.1117C>T (p.R373W) of LRP4, were tested in mammalian kidney and osteoblast cells. The results showed that LRP4 suppressed both Wnt/-Catenin and Notch signaling pathways, and these activities were perturbed either by LRP4 missense mutations or by a knockdown of LRP4. Our finding underscore that LRP4 is required for limiting Jagged-Notch signaling throughout the fin/limb and kidney development, whose perturbation representing a novel mechanism for LRP4-related diseases. Moreover, our study reveals an evolutionarily conserved relationship between LRP4 and Jagged-Notch signaling, which may shed light on how the Notch signaling is fine-tuned during fin/limb development.
KeywordSkeletogenesis Bone disorders Pronephros Morphant Phenocopy EGF-like domain wt1b HES1
DOI10.1007/s00018-018-2928-3
Funding OrganizationNatural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST)
Indexed BySCI ; SCI
Language英语
Funding ProjectNatural Science Foundation of Shaanxi Province, China[2016JM3018] ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China[2018FB10] ; Ministry of Science and Technology, Taiwan (MOST)[106-2313-B-029-002-MY3] ; Ministry of Science and Technology, Taiwan (MOST)[105-2313-B-029-002] ; Ministry of Science and Technology, Taiwan (MOST)[102-2628-B-029-002-MY3]
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000455367100010
WOS KeywordFRASER-SYNDROME ; RECEPTOR ; DIFFERENTIATION ; PROTEINS ; PATHWAY ; COMPLEX ; CELLS ; AGRIN
PublisherSPRINGER BASEL AG
Funding OrganizationNatural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Natural Science Foundation of Shaanxi Province, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Opening Foundation of State Key Laboratory of Freshwater Ecology and Biotechnology, China ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST) ; Ministry of Science and Technology, Taiwan (MOST)
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/28737
Collection其他_期刊论文
Corresponding AuthorTian, Jing; Liu, Yi-Wen
Affiliation1.Northwest Univ, Coll Life Sci, 229 Taibai North Rd, Xian 710069, Shaanxi, Peoples R China
2.Tunghai Univ, Dept Life Sci, 1727,Sec 4,Taiwan Blvd, Taichung 40704, Taiwan
3.Jordan Univ Sci & Technol, Dept Med Lab Sci, Irbid, Jordan
4.Natl Ctr Diabet Endocrinol & Genet, Amman, Jordan
5.Univ Jordan, Sch Med, Orthoped Div, Special Surg Dept, Amman, Jordan
6.State Key Lab Freshwater Ecol & Biotechnol, Wuhan, Hubei, Peoples R China
Recommended Citation
GB/T 7714
Tian, Jing,Shao, Jinhui,Liu, Cong,et al. Deficiency of lrp4 in zebrafish and human LRP4 mutation induce aberrant activation of Jagged-Notch signaling in fin and limb development[J]. CELLULAR AND MOLECULAR LIFE SCIENCES,2019,76(1):163-178.
APA Tian, Jing.,Shao, Jinhui.,Liu, Cong.,Hou, Hsin-Yu.,Chou, Chih-Wei.,...&Liu, Yi-Wen.(2019).Deficiency of lrp4 in zebrafish and human LRP4 mutation induce aberrant activation of Jagged-Notch signaling in fin and limb development.CELLULAR AND MOLECULAR LIFE SCIENCES,76(1),163-178.
MLA Tian, Jing,et al."Deficiency of lrp4 in zebrafish and human LRP4 mutation induce aberrant activation of Jagged-Notch signaling in fin and limb development".CELLULAR AND MOLECULAR LIFE SCIENCES 76.1(2019):163-178.
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
[Tian, Jing]'s Articles
[Shao, Jinhui]'s Articles
[Liu, Cong]'s Articles
Baidu academic
Similar articles in Baidu academic
[Tian, Jing]'s Articles
[Shao, Jinhui]'s Articles
[Liu, Cong]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Tian, Jing]'s Articles
[Shao, Jinhui]'s Articles
[Liu, Cong]'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.