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.
| Original language | English |
|---|---|
| Pages (from-to) | 191-198 |
| Number of pages | 8 |
| Journal | Developmental Biology |
| Volume | 369 |
| Issue number | 2 |
| DOIs | |
| State | Published - 15 Sep 2012 |
Bibliographical note
Funding Information:We are grateful to Lila Solnica-Krezel for her support during initial stages of this work and for valuable discussions. We thank Ela Knapik and Atsushi Sawada for advice on positional cloning, Jochen Wittbrodt for Medaka rx3 promoter construct, Didier Stainier for transgenic kdrl lines, Ze'ev Paroush Avihu Klar, Eli Keshet and Inbal laboratory members for discussions and critical reading of the manuscript. This research was supported by the Israel Science Foundation Grant no. 791/09 and a Research Career Development Award from the Israel Cancer Research Fund (A. I.) .
Keywords
- Coloboma
- Lmo2
- Ocular vasculature
- Optic fissure
- Zebrafish