Presence of chondroitin sulphate and requirement for heparan sulphate biosynthesis in the developing zebrafish inner ear.
Presence of chondroitin sulphate and requirement for heparan sulphate biosynthesis in the developing zebrafish inner ear.
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DOI：
10.3389/fcell.2022.959624
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
形成斑马鱼内耳半规管的上皮形态发生依赖于大的糖胺聚糖透明质酸的产生，这被认为有助于推动上皮突起进入耳囊腔的驱动力。蛋白聚糖也与耳的形态发生有关：编码蛋白聚糖核心蛋白的几个基因，以及合成和修饰其多糖链的酶，在发育中的斑马鱼内耳中表达。在这项研究中，我们证明了硫酸软骨素的高度特异性本地化的网站上皮突起生长在耳朵，目前之前的任何形态变形的上皮。硫酸软骨素染色也存在于耳石膜中，而耳石硫酸角质素呈强阳性。我们发现，硫酸乙酰肝素的生物合成是至关重要的正常上皮突起生长，耳石生长和拴系。在硫酸乙酰肝素水平降低，但继续产生透明质酸的ext2突变耳中，上皮突起是不成熟的，并且不能充分生长以满足和融合形成通常跨越耳腔的组织柱。硫酸软骨素染色和多功能蛋白聚糖B（硫酸软骨素蛋白聚糖核心蛋白基因）的表达在ext2突变耳的未融合突起中异常地保持在高水平。我们提出了一个野生型上皮投射生长模型，其中透明质酸和蛋白聚糖连接形成填充投射核心的水合凝胶，这两类分子在斑马鱼半规管形态发生中发挥重要作用。
Epithelial morphogenesis to form the semicircular canal ducts of the zebrafish inner ear depends on the production of the large glycosaminoglycan hyaluronan, which is thought to contribute to the driving force that pushes projections of epithelium into the lumen of the otic vesicle. Proteoglycans are also implicated in otic morphogenesis: several of the genes coding for proteoglycan core proteins, together with enzymes that synthesise and modify their polysaccharide chains, are expressed in the developing zebrafish inner ear. In this study, we demonstrate the highly specific localisation of chondroitin sulphate to the sites of epithelial projection outgrowth in the ear, present before any morphological deformation of the epithelium. Staining for chondroitin sulphate is also present in the otolithic membrane, whereas the otoliths are strongly positive for keratan sulphate. We show that heparan sulphate biosynthesis is critical for normal epithelial projection outgrowth, otolith growth and tethering. In the ext2 mutant ear, which has reduced heparan sulphate levels, but continues to produce hyaluronan, epithelial projections are rudimentary, and do not grow sufficiently to meet and fuse to form the pillars of tissue that normally span the otic lumen. Staining for chondroitin sulphate and expression of versican b, a chondroitin sulphate proteoglycan core protein gene, persist abnormally at high levels in the unfused projections of the ext2 mutant ear. We propose a model for wild-type epithelial projection outgrowth in which hyaluronan and proteoglycans are linked to form a hydrated gel that fills the projection core, with both classes of molecule playing essential roles in zebrafish semicircular canal morphogenesis.
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影响因子：
3.7
作者：
Habicher J;Haitina T;Eriksson I;Holmborn K;Dierker T;Ahlberg PE;Ledin J
通讯作者：
Ledin J
DOI：
10.1242/dev.098061
发表时间：
2013-11
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Geng FS;Abbas L;Baxendale S;Holdsworth CJ;Swanson AG;Slanchev K;Hammerschmidt M;Topczewski J;Whitfield TT
通讯作者：
Whitfield TT
影响因子：
3.4
作者：
Chang, Patrick S.;McLane, Louis T.;Curtis, Jennifer E.
通讯作者：
Curtis, Jennifer E.
影响因子：
3.4
作者：
Attili S;Richter RP
通讯作者：
Richter RP
DOI：
10.1002/dvdy.24195
发表时间：
2015-03
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
--
作者：
Lundberg YW;Xu Y;Thiessen KD;Kramer KL
通讯作者：
Kramer KL