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First published online 2 October 2008
doi: 10.1242/dev.028076
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1 Department of Molecular Biology and Genetics, Johns Hopkins University School
of Medicine, Baltimore, MD 21205, USA.
2 Department of Neuroscience, Johns Hopkins University School of Medicine,
Baltimore, MD 21205, USA.
3 Department of Ophthalmology, and the Johns Hopkins University School of
Medicine, Baltimore, MD 21205, USA.
4 Howard Hughes Medical Institute, Johns Hopkins University School of Medicine,
Baltimore, MD 21205, USA.
* Author for correspondence (e-mail: jnathans{at}jhmi.edu)
Accepted 1 September 2008
Microphthalmia, coloboma and persistent fetal vasculature within the
vitreous cavity are among the most common human congenital ocular anomalies,
and each has been associated with a variety of genetic disorders. Here we show
that, in the mouse, loss of frizzled 5 (Fz5) - a putative Wnt receptor
expressed in the eye field, optic cup and retina - causes all of these defects
with high penetrance. In the developing Fz5-/- eye, the
sequence of defects, in order of appearance, is: increased cell death in the
ventral retina, delayed and/or incomplete closure of the ventral fissure, an
excess of mesenchymal cells in the vitreous cavity, an excess of retinal
astrocyte precursors and mature astrocytes, and persistence of the hyaloid
vasculature in association with a large number of pigment cells.
Fz5-/- mice also exhibit a late-onset progressive retinal
degeneration by 
6 months of age, which might be related to the expression
of Fz5 in Müller glia in the adult retina. These results demonstrate a
central role for frizzled signaling in mammalian eye development and are
likely to be relevant to the etiology of congenital human ocular
anomalies.
Key words: Coloboma, frizzled 5 (Fz5; Fzd5), Microphthalmia, Optic fissure, PFV, Retinal degeneration
