Temporal characterization of optic fissure basement membrane composition suggests nidogen may be an initial target of remodeling
Temporal characterization of optic fissure basement membrane composition suggests nidogen may be an initial target of remodeling
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DOI：
10.1016/j.ydbio.2019.04.012
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发表时间：
2019-08-01
影响因子：
2.7
通讯作者：
Famulski, J. K.
中科院分区：
文献类型：
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作者：
Carrara, Nicholas;Weaver, Megan;Famulski, J. K.
视裂融合是完成视网膜形态发生和确保视柄正常功能所必需的。该事件的失败导致先天性缺损，这是儿童失明的主要原因之一。从机制上讲，广泛接受的是，成熟视网膜周围的基底膜（BM）需要在裂隙内重塑，以促进随后的上皮片融合。然而，驱动BM重塑的机制尚未阐明。作为理解这一关键分子事件的第一步，我们全面表征了斑马鱼胚胎视裂BM的核心组成。斑马鱼视裂BM表达层粘连蛋白a1、a4、b1a、c1和c3，巢蛋白1a、1b和2a，Ⅳ型胶原a1和a2以及串珠素。此外，我们观察到，层粘连蛋白，串珠素和IV型胶原蛋白的表达持续在裂缝融合过程中，高达56 hpf，而巢蛋白表达下调后开始融合，在36 hpf。使用免疫组化，我们还表明，巢蛋白被删除之前，层粘连蛋白的BM，表明重塑的BM是一个有序的事件。最后，我们的特点是视网膜形态发生的巢蛋白功能的情况下，并记录视网膜畸形类似于层粘连蛋白突变体中观察到的。综上所述，我们提出了一个模型，BM重塑巢蛋白作为一个关键在启动视裂融合。
Fusion of the optic fissure is necessary to complete retinal morphogenesis and ensure proper function of the optic stalk. Failure of this event leads to congenital coloboma, one of the leading causes of pediatric blindness. Mechanistically it is widely accepted that the basement membrane (BM) surrounding the maturing retina needs to be remodeled within the fissure in order to facilitate subsequent epithelial sheet fusion. However, the mechanism driving BM remodeling has yet to be elucidated. As a first step to understanding this critical molecular event we comprehensively characterized the core composition of optic fissure BMs in the zebrafish embryos. Zebrafish optic fissure BMs were found to express laminin a1, a4, b1a, c1 and c3, nidogen 1a, 1b and 2a, collagen IV a1 and a2 as well as perlecan. Furthermore, we observed that laminin, perlecan and collagen IV expression persists in the fissure during fusion, up to 56 hpf, while nidogen expression is downregulated upon initiation of fusion, at 36 hpf. Using immunohistochemistry we also show that nidogen is removed from the BM prior to that of laminin, indicating that remodeling of the BM is an ordered event. Lastly, we characterized retinal morphogenesis in the absence of nidogen function and documented retinal malformation similar to what is observed in laminin mutants. Taken together, we propose a model of BM remodeling where nidogen acts as a linchpin during initiation of optic fissure fusion.