Gestri Gaia, Bazin-Lopez Naiara, Scholes Clarissa, Wilson Stephen W
Division of Biosciences, Department of Cell and Developmental Biology, University College London, London, United Kingdom.
Front Cell Neurosci. 2018 Feb 20;12:42. doi: 10.3389/fncel.2018.00042. eCollection 2018.
Coloboma is a defect in the morphogenesis of the eye that is a consequence of failure of choroid fissure fusion. It is among the most common congenital defects in humans and can significantly impact vision. However, very little is known about the cellular mechanisms that regulate choroid fissure closure. Using high-resolution confocal imaging of the zebrafish optic cup, we find that apico-basal polarity is re-modeled in cells lining the fissure in proximal to distal and inner to outer gradients during fusion. This process is accompanied by cell proliferation, displacement of vasculature, and contact between cells lining the choroid fissure and periocular mesenchyme (POM). To investigate the role of POM cells in closure of the fissure, we transplanted optic vesicles onto the yolk, allowing them to develop in a situation where they are depleted of POM. The choroid fissure forms normally in ectopic eyes but fusion fails in this condition, despite timely apposition of the nasal and temporal lips of the retina. This study resolves some of the cell behaviors underlying choroid fissure fusion and supports a role for POM in choroid fissure fusion.
脉络膜缺损是一种眼部形态发生缺陷,是脉络膜裂融合失败的结果。它是人类最常见的先天性缺陷之一,会对视力产生重大影响。然而,对于调节脉络膜裂闭合的细胞机制,我们知之甚少。通过对斑马鱼视杯进行高分辨率共聚焦成像,我们发现,在融合过程中,裂隙内衬细胞的顶-基极性在从近端到远端、从内侧到外侧的梯度中重新塑造。这一过程伴随着细胞增殖、脉管系统移位以及脉络膜裂内衬细胞与眼周间充质(POM)之间的接触。为了研究POM细胞在裂隙闭合中的作用,我们将视泡移植到卵黄上,使其在缺乏POM的情况下发育。尽管视网膜鼻侧和颞侧边缘及时对合,但在异位眼中脉络膜裂正常形成,但在这种情况下融合失败。这项研究揭示了脉络膜裂融合背后的一些细胞行为,并支持POM在脉络膜裂融合中的作用。