Webber CA et al. (2003), Fibroblast growth factors redirect retinal axon...

XB-ART-4531

Dev Biol 2003 Nov 01;2631:24-34. doi: 10.1016/s0012-1606(03)00435-4.

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Fibroblast growth factors redirect retinal axons in vitro and in vivo.

Webber CA , Hyakutake MT , McFarlane S .

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Growth factors have been shown previously to participate in the process of axon target recognition. We showed that fibroblast growth factor receptor (FGFR) signaling is required for Xenopus laevis retinal ganglion cell (RGC) axons to recognize their major midbrain target, the optic tectum [neuron 17 (1996), 245]. Therefore, we have hypothesized that a change in expression of a fibroblast growth factor (FGF) at the entrance of the optic tectum, the border between the diencephalon and mesencephalon, may serve as a signal to RGC axons that they have reached their target. To determine whether RGC axons can sense changes in FGF levels, we asked whether they altered their behavior upon encountering an ectopic source of FGF. We found that in vivo RGC growth cones avoided FGF-misexpressing cells along their path, and that FGF-2 directly repelled RGC growth cones in an in vitro growth cone turning assay. These data support the idea that RGC axons can sense changes in FGF levels, and as such provide a mechanism by which FGFR signaling is involved in RGC axon target recognition.

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Species referenced: Xenopus laevis
Genes referenced: fgf2 fgf4 tec XB5802829
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	Fig. 1. RGC axons avoid FGF-misexpressing cells in vivo. Whole-mount stage 40 Xenopus embryo brains shown from a lateral view. Representative examples of the behavior of HRP-labeled RGC axons (red) encountering either GFP (A–B), or GFP and eFGF (C–F) plasmid-expressing brain cells (green). (B) and (D) are higher power views of boxed areas in (A) and (C), respectively. Brain cells transfected with both GFP and eFGF plasmids appear to have differentiated and exhibit processes (arrows). Tec, tectum; ot, optic tract; Tel, telencephalon; Di, diencephalon; A, anterior; D, dorsal. Scale bar in (A) is 50 m for (A, C, and E). Scale bar in (B) is 25 m for (B, D, and F).
	Fig. 2. GFP-positive cells cotransfected with the FGF-2 cDNA plasmid reliably misexpress the FGF-2 transgene. (A–B) Lateral views of whole-mount stage 40 Xenopus brains transfected with GFP (A) or FGF-2 (B) plasmid at stage 24. HRP-labeled optic projections ignore GFP-misexpressing cells (arrowhead in A), but avoid an FGF-2-misexpressing cell (arrowheads in B). (C–D) Transverse sections through the eyes and brain of a stage 33/34 embryo transfected at stage 19 with GFP and FGF-2 cDNA plasmids. The majority of GFP-positive cells (C) are also immunolabeled with an antibody that recognizes Xenopus FGF-2-misexpressing cells (D). Tec, tectum; ot, optic tract; Di, diencephalon; R, retina; D, dorsal; A, anterior; V, ventral. Scale bar in (A) is 50 m for (A–B). Scale bar in (C) is 25 m for (C–D).
	Fig. 3. A non-FGF FGFR ligand also redirects RGC axons. (A–E) Lateral views of whole-mount Xenopus brains transfected with GFP (A), or GFP and FRL-2 (B–E) cDNA plasmids at stage 19. HRP-labeled RGC axons (red) ignored neuroepithelial cells misexpressing GFP (A, green), but avoided crossing over the GFP and FRL-2-misexpressing cells (B and C, green). (C) shows the overlay of photomicrographs of the HRP-labeled optic tract (D) and the GFP/FRL2- misexpressing cell (E). (F) Graph showing the percentage of optic projections that deviated around transfected cells misexpressing GFP alone (n 14), GFP and eFGF (n 11), FGF-2 (n 10), and GFP and FRL-2 (n 8). Only cells misexpressing an FGFR ligand affected the RGC optic projection. D, dorsal; A, anterior; ot, optic tract. Scale bar is 25 m for (A, C–E). Scale bar in (B) is 50 m.
	Fig. 4. FGF-misexpressing cells are postmitotic. Twenty micrometer transverse sections through the eyes and midbrain of Xenopus embryos transfected at stage 19 with GFP, or GFP and eFGF plasmids (green), and injected with BrdU at stage 33/34. After 2 h, stage 35/36 embryos were fixed, sectioned, and processed for BrdU immunocytochemistry (red). Few neuroepithelial cells misexpressing GFP (A), or GFP and eFGF (B), were BrdU-positive. Mb, midbrain; R, retina; D, dorsal; V, ventral; Ve, ventricle. Scale bar is 50 m for (A–B).