Hyaloid vasculature and mmp2 activity play a role during optic fissure fusion in zebrafish.
Hyaloid vasculature and mmp2 activity play a role during optic fissure fusion in zebrafish.
复制标题
玻璃体脉管系统和 mmp2 活性在斑马鱼视裂融合过程中发挥作用。
DOI：
10.1038/s41598-020-66451-6
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发表时间：
2020
影响因子：
4.6
通讯作者：
Famulski,JakubK
中科院分区：
文献类型：
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作者：
Weaver,MeganL;Piedade,WarlenP;Meshram,NishitaN;Famulski,JakubK
脊椎动物视网膜的发育需要视裂（OF）的及时和精确的融合。该事件失败导致缺损形式的先天性视力损害。最近的研究表明玻璃体血管参与OF融合。为了研究这种联系，我们分析了斑马鱼pax 2a noi突变系中的OF融合和玻璃体血管发生。我们首先确定pax 2a −/−胚胎在基底膜（BM）降解之前未能在OF中积累F-肌动蛋白。此外，使用3D和实时成像，我们观察到pax 2a −/−胚胎中的玻璃体血管化减少。当检查pax 2a功能丧失和玻璃体血管之间的联系时，我们观察到玻璃体血管的调节因子talin 1表达显著减少。此外，在pax 2a −/−胚胎中发现颅骨VEGF表达减少。VEGF信号传导的药理学抑制表现为pax 2a −/−脉管系统、F-肌动蛋白和BM降解表型。最后，我们确定OF相关的玻璃体血管是mmp 2、mmp 14 a和mmp 14 b表达的来源，并表明mmp 2在功能上是OF BM降解所必需的。综上所述，我们提出了一种pax 2a驱动的机制，确保适当和及时的玻璃体脉管系统入侵的OF，以促进BM重塑mmp 2的可用性。
Vertebrate retinal development requires timely and precise fusion of the optic fissure (OF). Failure of this event leads to congenital vision impairment in the form of coloboma. Recent studies have suggested hyaloid vasculature to be involved in OF fusion. In order to examine this link, we analyzed OF fusion and hyaloid vasculogenesis in the zebrafish pax2a noi mutant line. We first determined that pax2a−/−embryos fail to accumulate F-actin in the OF prior to basement membrane (BM) degradation. Furthermore, using 3D and live imaging we observed reduced OF hyaloid vascularization in pax2a−/−embryos. When examining the connection between pax2a loss of function and hyaloid vasculature, we observed significant reduction oftalin1expression, a regulator of hyaloid vasculature. In addition, cranial VEGF expression was found to be reduced in pax2a−/−embryos. Pharmacological inhibition of VEGF signaling phenocopied the pax2a−/−vasculature, F-actin and BM degradation phenotypes. Lastly, we determined that OF associated hyaloid vasculature is a source ofmmp2, mmp14a and mmp14bexpression and showed that mmp2 is functionally necessary for degradation of OF BM. Taken together we propose a pax2a driven mechanism that ensures proper and timely hyaloid vasculature invasion of the OF in order to facilitate availability of the BM remodeler mmp2.