ECM alterations in Fndc3a (Fibronectin Domain Containing Protein 3A) deficient zebrafish cause temporal fin development and regeneration defects
ECM alterations in Fndc3a (Fibronectin Domain Containing Protein 3A) deficient zebrafish cause temporal fin development and regeneration defects
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DOI：
10.1038/s41598-019-50055-w
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发表时间：
2019-09-16
影响因子：
4.6
通讯作者：
Klopocki, Eva
中科院分区：
文献类型：
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作者：
Liedtke, Daniel;Orth, Melanie;Klopocki, Eva
鳍的发育和再生是与硬骨鱼高度相关的复杂生物过程。它们共享遗传因素、信号通路和细胞特性，以协调规则形状的四肢的形成。尤其是由细胞外基质(ECM)的形成定义的正确的组织结构是至关重要的。基因表达和蛋白质定位研究表明，fndc3a(含纤维连接蛋白结构域的蛋白3a)在斑马鱼尾鳍的发育和再生中均有表达。我们通过CRISPR/Cas9建立了一个亚型fndc3a突变系(fndc3a(W)(ue1/wue1))，在中鳍折叠发育的早期表现出表型畸形和基因表达模式的变化。这些发育影响大多是暂时的，但会导致一小部分成年人的尾鳍永久变形。此外，成年fndc3a(W)(Ue1)(/wue1)突变体的尾鳍再生受到对放线菌形成和表皮细胞组织的干扰。对ECM的研究表明，表皮组织结构的丧失是这两种观察到的缺陷的共同原因。因此，我们的结果提供了这些发育过程之间的分子联系，并预示着Fndc3a在斑马鱼肢体发育和再生过程中是一种新的表皮细胞特性的时间调节因子。
Fin development and regeneration are complex biological processes that are highly relevant in teleost fish. They share genetic factors, signaling pathways and cellular properties to coordinate formation of regularly shaped extremities. Especially correct tissue structure defined by extracellular matrix (ECM) formation is essential. Gene expression and protein localization studies demonstrated expression of fndc3a (fibronectin domain containing protein 3a) in both developing and regenerating caudal fins of zebrafish (Danio rerio). We established a hypomorphic fndc3a mutant line (fndc3a(w)(ue1/wue1)) via CRISPR/Cas9, exhibiting phenotypic malformations and changed gene expression patterns during early stages of median fin fold development. These developmental effects are mostly temporary, but result in a fraction of adults with permanent tail fin deformations. In addition, caudal fin regeneration in adult fndc3a(w)(ue1)(/wue1) mutants is hampered by interference with actinotrichia formation and epidermal cell organization. Investigation of the ECM implies that loss of epidermal tissue structure is a common cause for both of the observed defects. Our results thereby provide a molecular link between these developmental processes and foreshadow Fndc3a as a novel temporal regulator of epidermal cell properties during extremity development and regeneration in zebrafish.