Abnormal vasculature interferes with optic fissure closure in lmo2 mutant zebrafish embryos

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Coloboma / embryology
  • Coloboma / genetics
  • DNA Primers / genetics
  • Eye / blood supply
  • Eye / enzymology
  • Eye Abnormalities / embryology*
  • Eye Abnormalities / genetics*
  • Gene Expression Regulation, Developmental
  • LIM Domain Proteins / genetics*
  • Mutation
  • Phenotype
  • Retinal Vessels / abnormalities
  • Retinal Vessels / embryology
  • Transcription Factors / genetics*
  • Zebrafish / embryology*
  • Zebrafish / genetics*
  • Zebrafish Proteins / genetics*


  • DNA Primers
  • LIM Domain Proteins
  • Transcription Factors
  • Zebrafish Proteins
  • lmo2 protein, zebrafish