Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Dev Biol. 2012 Sep 15;369(2):191-8. doi: 10.1016/j.ydbio.2012.06.029. Epub 2012 Jul 20.
Ocular coloboma is a potentially blinding congenital eye malformation caused by failure of optic fissure closure during early embryogenesis. The optic fissure is a ventral groove that forms during optic cup morphogenesis, and through which hyaloid artery and vein enter and leave the developing eye, respectively. After hyaloid artery and vein formation, the optic fissure closes around them. The mechanisms underlying optic fissure closure are poorly understood, and whether and how this process is influenced by hyaloid vessel development is unknown. Here we show that a loss-of-function mutation in lmo2, a gene specifically required for hematopoiesis and vascular development, results in failure of optic fissure closure in zebrafish. Analysis of ocular blood vessels in lmo2 mutants reveals that some vessels are severely dilated, including the hyaloid vein. Remarkably, reducing vessel size leads to rescue of optic fissure phenotype. Our results reveal a new mechanism leading to coloboma, whereby malformed blood vessels interfere with eye morphogenesis.
眼脑裂畸形是一种潜在致盲性的先天性眼部畸形，由胚胎早期视裂未能闭合引起。视裂是视杯形态发生过程中形成的一个腹侧沟，脉络膜血管通过这个沟进入和离开正在发育的眼球。脉络膜血管形成后，视裂围绕着它们闭合。视裂闭合的机制尚不清楚，也不知道这个过程是否以及如何受脉络膜血管发育的影响。在这里，我们发现造血和血管发育特异必需的基因 lmo2 的功能丧失突变导致斑马鱼的视裂闭合失败。对 lmo2 突变体眼部血管的分析表明，一些血管严重扩张，包括脉络膜静脉。值得注意的是，减小血管大小可挽救视裂表型。我们的结果揭示了导致脑裂畸形的一个新机制，即畸形血管干扰了眼球形态发生。
