Spatio‐temporal distribution of acidic and basic FGF indicates a role for FGF in rat lens morphogenesis

Abstract

As part of an investigation into the role FGF in lens development, we have studied the distribution of both aFGF and bFGF during eye morphogenesis from embryonic days 10 to 18 (E10–E18) in the rat. For aFGF, reactivity was found only in ectoderm at E10, prior to contact between the optic vesicle and presumptive lens ectoderm. During lens placode formation (E11) there was a transient, diffuse reactivity for aFGF in anterior optic vesicle cells directly apposed to the labelled ectoderm of the lens placode. At E12 the diffuse reactivity of the lens placode had changed to a discrete localisation along the basolateral surfaces of differentiating cells in the lens pit. Similar reactivity was associated with neuroblasts along the inner margin of the optic cup. At the early lens vesicle stage (E13) the baso‐lateral aFGF‐like reactivity associated with elongating lens cells was more intense and extensive. From the late lens vesicle stage (E14) to E18, reactivity in the lens was increasingly restricted to the equatorial regions which incorporate the germinative and transitional zones. From E16 to E18, aFGF‐like reactivity in the retina was predominantly localised in the peripheral regions corresponding to the developing ciliary body and iris and in the central retina associated with ganglion cell axons. For bFGF, weak reactivity was detectable as early as E13 in the developing lens capsule and increased in intensity during lens development with the posterior capsule reacting more intensely than the anterior capsule. Retinal bFGF‐like reactivity was first detected at E14, associated with differentiating ganglion cells in the central retina. From E16 to E18 the retinal ganglion cells showed increasing reactivity and the pattern of reactivity followed the centro‐peripheral pattern of retinal development. Thus reactivity for aFGF is first detected in presumptive lens ectoderm and subsequently in optic vesicle cells which are closely associated with lens ectoderm. This raises the possibility that aFGF may be involved in inductive interactions between presumptive lens ectoderm and optic vesicle. Furthermore the localisation patterns established for both aFGF and bFGF during lens and retina morphogenesis suggest an important role for FGF in regulating their morphogenesis and growth. © 1993 Wiley‐Liss, Inc.

Retinal stem cells and regeneration

“…Since several different FGFs are expressed in the developing eye-in the presumptive lens ectoderm and the optic stalk, as well as in the developing ciliary epithelium-it is likely that some redundancy exists in this system (see de Iongh and McAvoy, 1993;McCabe et al, 1999, for review;Vogel-Hopker et al, 2000). Thus, it has been difficult to demonstrate a requirement for FGF in the development of the neural retinal fate.…”

Heparan sulfate biosynthetic geneNdst1is required for FGF signaling in early lens development

“…Based on previous reports of FGF expression patterns, we extended our analysis to FGF1,2,3,5,8,9 and 15 to assay their pairwise interactions with FGFR1b, 1c, 2b, 2c, 3b, 3c and 4 (Chow and Lang, 2001;de Iongh and McAvoy, 1993;Kitaoka et al, 1994;Lovicu and Overbeek, 1998;Martinez-Morales et al, 2005;McWhirter et al, 1997;Nguyen and Arnheiter, 2000;Vogel-Hopker et al, 2000;Zhao et al, 2001). This includes all the FGF and FGFR variants known to be present during early eye development.…”

Targeted expression of the dominant-negative FGFR4a in the eye usingXrx1Aregulatory sequences interferes with normal retinal development

“…The formation of these cells types, and their correct proportionality, is necessary for the proper function of the vertebrate eye. FGF molecules and their receptors are expressed in developing retina (de Iongh and McAvoy, 1993;Gao and Hollyfield, 1995;McFarlane et al, 1998;Patstone et al, 1993), and several studies have investigated their role in proliferation, survival and differentiation of retinal cells (Guillemot and Cepko, 1992;Park and Hollenberg, 1989;Sievers et al, 1987). It was shown that inhibition of the FGFR1-mediated pathway in Xenopus embryos resulted in a 50% loss of photoreceptor and amacrine cells, with a concomitant increase of Müller cells (McFarlane et al, 1998).…”