脊椎动物眼原基由假复层神经上皮组成,视神经囊泡(OV),其中细胞获得神经视网膜或视网膜色素上皮(RPE)的命运。随着这些命运的出现,OV呈杯形,受神经视网膜内产生的机械力的影响。RPE是否被动地适应视网膜变化或主动地促进OV形态发生仍有待探索。我们产生了斑马鱼Tg(E1-bhlhe40:GFP)系以追踪RPE形态发生并询问其参与OV折叠的情况。我们证明,在几乎没有扩散的情况下,RPE细胞伸展和展平,从而匹配视网膜曲率并促进OV折叠。对RPE细胞骨架的局部干扰破坏组织拉伸和OV折叠。因此,极端的RPE平坦化和加速分化是快速发展的物种采用的有效解决方案,可以及时形成视杯。这种机制在羊膜中有所不同,其中增殖驱动RPE扩增,细胞平坦化的需求大大降低。
圆形眼球有助于优化视力——但是它们是如何获得独特的形状的呢?包括人类,眼睛在发育早期开始形成。称为视囊泡的单层胚胎组织重新组织成两层结构:薄的细胞外层,称为视网膜色素上皮(简称RPE),和一个更厚的内层称为神经视网膜。如果此过程失败,动物可能天生失明或视力受损。这种扁平的两层结构如何变成圆形仍在研究中。在鱼中,研究表明,内部细胞层-神经视网膜-产生机械力,导致发育中的组织向内弯曲,形成杯状形状。但目前尚不清楚细胞外层(RPE)是否也促成了这一过程。Moreno-Marmol等人。能够通过基因修饰斑马鱼使所有新的RPE细胞发荧光来研究这个问题。在显微镜下斑马鱼眼的早期发育之后,RPE细胞将自己展平成细长的结构,从而覆盖整个神经视网膜。这种变化是通过细胞内部骨骼重组而实现的。事实上,阻止这种重组阻止了RPE细胞变平,并阻止光学杯获得其弯曲形状。因此,结果证实了RPE在产生曲率中的直接作用。整个过程不需要RPE来产生新的细胞,允许弯曲的形状在几个小时内出现。这是斑马鱼等快速发展的物种的主要优势。在胚胎发育较慢的物种中,比如老鼠和人类,相反,RPE通过产生额外的细胞来生长-这个过程需要很多天。因此,眼睛的发展表明了各种物种如何使用不同的进化方法来实现共同的目标。
The vertebrate eye primordium consists of a pseudostratified neuroepithelium, the optic vesicle (OV), in which cells acquire neural retina or retinal pigment epithelium (RPE) fates. As these fates arise, the OV assumes a cup shape, influenced by mechanical forces generated within the neural retina. Whether the RPE passively adapts to retinal changes or actively contributes to OV morphogenesis remains unexplored. We generated a zebrafish Tg(E1-bhlhe40:GFP) line to track RPE morphogenesis and interrogate its participation in OV folding. We show that, in virtual absence of proliferation, RPE cells stretch and flatten, thereby matching the retinal curvature and promoting OV folding. Localized interference with the RPE cytoskeleton disrupts tissue stretching and OV folding. Thus, extreme RPE flattening and accelerated differentiation are efficient solutions adopted by fast-developing species to enable timely optic cup formation. This mechanism differs in amniotes, in which proliferation drives RPE expansion with a much-reduced need of cell flattening.
Rounded eyeballs help to optimize vision – but how do they acquire their distinctive shape? In animals with backbones, including humans, the eye begins to form early in development. A single layer of embryonic tissue called the optic vesicle reorganizes itself into a two-layered structure: a thin outer layer of cells, known as the retinal pigmented epithelium (RPE for short), and a thicker inner layer called the neural retina. If this process fails, the animal may be born blind or visually impaired. How this flat two-layered structure becomes round is still being investigated. In fish, studies have shown that the inner cell layer – the neural retina – generates mechanical forces that cause the developing tissue to curve inwards to form a cup-like shape. But it was unclear whether the outer layer of cells (the RPE) also contributed to this process. Moreno-Marmol et al. were able to investigate this question by genetically modifying zebrafish to make all new RPE cells fluoresce. Following the early development of the zebrafish eye under a microscope revealed that RPE cells flattened themselves into long thin structures that stretched to cover the entire neural retina. This change was made possible by the cell’s internal skeleton reorganizing. In fact, preventing this reorganization stopped the RPE cells from flattening, and precluded the optic cup from acquiring its curved shape. The results thus confirmed a direct role for the RPE in generating curvature. The entire process did not require the RPE to produce new cells, allowing the curved shape to emerge in just a few hours. This is a major advantage for fast-developing species such as zebrafish. In species whose embryos develop more slowly, such as mice and humans, the RPE instead grows by producing additional cells – a process that takes many days. The development of the eye thus shows how various species use different evolutionary approaches to achieve a common goal.