title: Gradients of cone differentiation and FGF expression during development of the foveal depression in macaque retina.
abstract: Cones in the foveola of adult primate retina are narrower and more elongated than cones on the foveal rim, which in turn, are narrower and more elongated than those located more eccentric. This gradient of cone morphology is directly correlated with cone density and acuity. Here we investigate the hypothesis that fibroblast growth factor (FGF) signaling mediates the morphological differentiation of foveal cones--in particular, the mechanism regulating the elongation of foveal cones. We used immunoreactivity to FGF receptor (R) 4, and quantitative analysis to study cone elongation on the horizontal meridian of macaque retinae, aged between foetal day (Fd) 95 and 2.5 years postnatal (P 2.5 y). We also used in situ hybridization and immunohistochemistry to investigate the expression patterns of FGF2 and FGFR1-4 at the developing fovea, and three other sample locations on the horizontal meridian. Labeled RNA was detected using the fluorescent marker "Fast Red" (Roche) and levels of expression in cone inner segments and in the ganglion cell layer (GCL) were compared using confocal microscopy, optical densitometry, and tested for statistical significance. Our results show that morphological differentiation of cones begins near the optic disc around Fd 95, progressing toward the developing fovea up until birth, approximately. Levels of FGF2 and FGFR4 mRNAs expression are low in foveal cones, compared with cones closer to the optic disc, during this period. There is no similar gradient of FGF2 mRNA expression in the ganglion cell layer of the same sections. Maturation of foveal cones is delayed until the postnatal period. The results suggest that a wave of cone differentiation spreads from the disc region toward the developing fovea during the second half of gestation in the macaque. A gradient of expression of FGFR4 and FGF2 associated with the wave of differentiation suggests that FGF signalling mediates cone narrowing and elongation.
authors.affiliation: Department of Ophthalmology and Save Sight Institute, University of Sydney, NSW 2006, Australia.
authors.forename: Elisa E
authors.initials: EE
authors.lastname: Cornish
authors.forename: Michele C
authors.initials: MC
authors.lastname: Madigan
authors.forename: Riccardo
authors.initials: R
authors.lastname: Natoli
authors.forename: Angela
authors.initials: A
authors.lastname: Hales
authors.forename: Anita E
authors.initials: AE
authors.lastname: Hendrickson
authors.forename: Jan M
authors.initials: JM
authors.lastname: Provis
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D048429:Cell Size; D004622:Embryo, Mammalian; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005584:Fovea Centralis / Q000166:cytology* / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008251:Macaca; D012333:RNA, Messenger / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000145:classification / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors