title: Abnormal vasculature interferes with optic fissure closure in lmo2 mutant zebrafish embryos.
abstract: 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.
authors: Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors: Omri
authors: O
authors: Weiss
authors: Rivka
authors: R
authors: Kaufman
authors: Natali
authors: N
authors: Michaeli
authors: Adi
authors: A
authors: Inbal
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D003103:Coloboma / Q000196:embryology / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005123:Eye / Q000098:blood supply / Q000201:enzymology; D005124:Eye Abnormalities / Q000196:embryology* / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D060588:LIM Domain Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D012171:Retinal Vessels / Q000002:abnormalities / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D017931:DNA Primers; D060588:LIM Domain Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C513186:lmo2 protein, zebrafish