1 Department of Molecular Embryology, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg , 79104 Freiburg , Germany.
2 Faculty of Biology, University of Freiburg , Schaenzlestrasse 1, 79104 Freiburg , Germany.
Open Biol. 2019 Feb 28;9(2):180179. doi: 10.1098/rsob.180179.
Optic cup morphogenesis is an intricate process. Especially, the formation of the optic fissure is not well understood. Persisting optic fissures, termed coloboma, are frequent causes for congenital blindness. Even though the defective fusion of the fissure margins is the most acknowledged reason for coloboma, highly variable morphologies of coloboma phenotypes argue for a diverse set of underlying pathomechanisms. Here, we investigate optic fissure morphogenesis in zebrafish to identify potential morphogenetic defects resulting in coloboma. We show that the formation of the optic fissure depends on tissue flow movements, integrated into the bilateral distal epithelial flow forming the optic cup. On the temporal side, the distal flow translates into a ventral perpendicular flow, shaping the temporal fissure margin. On the nasal side, however, the distal flow is complemented by tissue derived from the optic stalk, shaping the nasal fissure margin. Notably, a distinct population of TGFβ-signalling positive cells is translocated from the optic stalk into both fissure margins. Furthermore, we show that induced BMP signalling as well as Wnt-signalling inhibition result in morphogenetic defects of the optic fissure. Our data also indicate that morphogenesis is crucial for a proper positioning of pre-specified dorsal-ventral optic cup domains.
视杯形态发生是一个复杂的过程。特别是，视裂的形成还不太清楚。持续存在的视裂，称为裂孔畸形，是先天性失明的常见原因。尽管裂缘缺陷融合是裂孔畸形最公认的原因，但裂孔畸形表型的高度可变形态表明存在多种潜在的发病机制。在这里，我们研究了斑马鱼的视裂形态发生，以确定导致裂孔畸形的潜在形态发生缺陷。我们表明，视裂的形成取决于组织流动运动，这些运动整合到形成视杯的双侧远端上皮流中。在颞侧，远端流转化为一个向腹侧的垂直流，形成颞侧裂缘。然而，在鼻侧，远端流由来自视柄的组织补充，形成鼻侧裂缘。值得注意的是，一群独特的 TGFβ 信号阳性细胞从视柄迁移到两个裂缘。此外，我们还表明，诱导的 BMP 信号以及 Wnt 信号抑制会导致视裂的形态发生缺陷。我们的数据还表明，形态发生对于预先指定的背-腹视杯域的正确定位至关重要。
