Growth and Differentiation of the Retina and the Optic Tectum in the Medaka Fish Requires olSfrp5

Secreted Frizzled-Related Proteins (SFRPs) are extracellular modulators of Wnt and Bmp signaling. Previous studies in birds and fishes have shown that Sfrp1, a member of this family, is strongly expressed throughout the development of the eye contributing to the specification of the eye field, retina neurogenesis and providing guidance information to retina ganglion cell axons. Here, we report that in medaka fish (Oryzias latipes) the expression of olSfrp5, which is closely related to olSfrp1, largely overlaps with that of olSfrp1 in the eye, but is additionally expressed in the developing midbrain and gut primordium. Morpholino-based interference with olSfrp5 expression causes microphthalmia and reduction of the tectum size associated with an increase in apoptotic cell death in these structures. Furthermore, interference with the levels of olSfrp5 expression impairs the patterning of the ventral portion of the optic cup, leading in some cases to a fissure coloboma. These early defects are followed by an abnormal retinal and tectal neurogenesis. In particular, only reduced numbers of photoreceptor and RGC were generated in olSfrp5 morphants retinas. The results point to an important role of olSfrp5 in visual system formation and indicate that olSfrp1 and olSfrp5, despite their overlapping expression, have only partially redundant function during eye development. (C) 2009 Wiley Periodicals, Inc. Develop Neurobiol 69: 617-632, 2009