The Role of Low Density Lipoprotein Receptor-Related Protein 4 for the Fin and Kidney Development in Zebrafish

• Main Authors: Hsin-Yu Hou, 侯欣雨
• Other Authors: Yi-Wen Liu
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/45876027678321415663

碩士 === 東海大學 === 生命科學系 === 105 === The Cenani-Lenz syndrome is a human recessive genetic disease which is caused by the mutation oflow density lipoprotein receptor-related protein 4 (LRP4) gene. The clinical features of this disease are syndactyly and kidney hypoplasia. In mice, Lrp4 mutation also causes syndactyly, kidney malformations and tooth defects. Lrp4 protein is an antagonist which can inhibit activation of Wnt/β-catenin pathway. In order to explore whether zebrafish can be established as a disease model of Cenani-Lenz syndrome, we identified the zebrafish homolog of mammalian LRP4. In our study, zebrafish embryos injected with antisense morpholinos against lrp4 demonstrated abnormal morphogenesis of the kidney, stunt pectoral fins, as well as severe cyst formations in the fin fold and the caudal vein plexus. Interestingly, we found that there was abnormal blood accumulation at the caudal vein plexus. In the lrp4 MO-injected Tg(kdrl:GFP)s843embryo, the development of the pectoral fin was defective, and there was a swollen lumen at the caudal vein plexus. Notably, the lrp4 morphant and mutant phenocopied the human Cenani-Lenz syndrome in terms of limb/fin development. On the other hand, the phenotype of embryonic fin fold and kidney in thelrp4 morphant could be rescued by injecting mouse Lrp4 mRNA. It suggests that the Lrp4-mediated pathway is highly conserved among vertebrates. Using Tg(Tcf/Lef-miniP:dGFP)reporter lines to quantify the Wnt signal activity, there was however no significant elevation of Wnt reporter activity in the lrp4 morphant. To further explore the role of zebrafish lrp4 for regulating the Wnt/β-catenin pathway, I will use real-time RT-PCR to analyze the expression of responsive genes of Wnt/β-catenin pathway.