Zebrafish otolith biomineralization requires polyketide synthase.
Zebrafish otolith biomineralization requires polyketide synthase.
复制标题
斑马鱼耳石生物矿化需要聚酮合酶。
DOI：
10.1016/j.mod.2019.04.001
复制
发表时间：
2019
影响因子：
2.6
通讯作者：
Kramer,KennethL
中科院分区：
文献类型：
--
作者：
Thiessen,KevinD;Grzegorski,StevenJ;Chin,Yvonne;Higuchi,LisaN;Wilkinson,ChristopherJ;Shavit,JordanA;Kramer,KennethL
附着在前庭毛细胞上的偏折生物矿化晶体对于维持平衡是必要的。斑马鱼（Danio rerio）是研究这些被称为耳石的生物矿化晶体的有用生物，因为许多所需的基因与人类耳锥发育同源。我们试图在三个纯合隐性突变体中鉴定和描述致病基因，即no content（nco）、corkscrew（csr）和vns（vns），这些突变体在早期穗发育过程中不能发育耳石。我们发现nco，csr和vns在聚酮合酶（pks 1）中有潜在的有害突变，pks 1是一种多模块蛋白，以前在脊索动物和棘皮动物中的生物矿化事件中有牵连。我们发现，耳锥蛋白-90（Oc 90）的表达在耳囊内是弥漫性的，因此，它是不足以在斑马鱼的耳石生物矿化。同样，耳凝胶蛋白（耳石膜中耳石束缚所需的蛋白质）的正常定位不足以实现Oc 90附着。此外，eNOS信号通路和内皮素-1信号通路分别是耳石发育不全过程中上调和下调最多的通路。我们的研究结果表明，不同的过程中的脊椎动物的耳石成核和生物矿化，并将是一个起点的模型是独立的OC 90介导的播种。本研究为进一步研究eNOS信号和内皮素-1信号在耳石形成中的作用奠定了基础。
Deflecting biomineralized crystals attached to vestibular hair cells are necessary for maintaining balance. Zebrafish (Danio rerio) are useful organisms to study these biomineralized crystals called otoliths, as many required genes are homologous to human otoconial development. We sought to identify and characterize the causative gene in a trio of homozygous recessive mutants,no content(nco) andcorkscrew(csr), andvanished(vns), which fail to develop otoliths during early ear development. We show thatnco,csr, andvnshave potentially deleterious mutations in polyketide synthase (pks1), a multi-modular protein that has been previously implicated in biomineralization events in chordates and echinoderms. We found that Otoconin-90 (Oc90) expression within the otocyst is diffuse inncoandcsr; therefore, it is not sufficient for otolith biomineralization in zebrafish. Similarly, normal localization of Otogelin, a protein required for otolith tethering in the otolithic membrane, is not sufficient for Oc90 attachment. Furthermore, eNOS signaling and Endothelin-1 signaling were the most up- and down-regulated pathways during otolith agenesis innco, respectively. Our results demonstrate distinct processes for otolith nucleation and biomineralization in vertebrates and will be a starting point for models that are independent of Oc90-mediated seeding. This study will serve as a basis for investigating the role of eNOS signaling and Endothelin-1 signaling during otolith formation.