Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
The embryonic chick is able to regenerate the retina after it has been removed. We have previously shown that proliferating stem/progenitor cells present in the ciliary body/ciliary marginal zone (CB/CMZ) of the chick eye are responsible for regeneration, which can be induced by ectopic fibroblast growth factor-2 (FGF2) or Sonic hedgehog (Shh). Here, we reveal the mechanisms showing how FGF2 and Shh signaling are interdependent during retina regeneration. If the FGF pathway is inhibited, regeneration stimulated by Shh is inhibited. Likewise, if the Hedgehog pathway is inhibited, regeneration stimulated by FGF2 is inhibited. We examined early signaling events in the CB/CMZ and found that FGF2 or Shh induced a robust Erk phosphorylation during the early stages of retina regeneration. Shh also up-regulated the expression of several members of the FGF signaling pathway. We show that ectopic FGF2 or Shh overexpression increased the number of phosphohistone 3 (PH3)-positive cells in the CB/CMZ and inhibition of either pathway decreased the number of PH3-positive cells. Additionally, both FGF and Hh signaling are required for cell survival in the CB/CMZ, whereas Hh and not FGF signaling plays a role in maintaining the identity of the retinal progenitor population in this region. Combined, our results support a model where the FGF and Hedgehog pathways work together to stimulate retina regeneration.
Agius,
Converse control of oligodendrocyte and astrocyte lineage development by Sonic hedgehog in the chick spinal cord.
2004, Pubmed
Agius,
Converse control of oligodendrocyte and astrocyte lineage development by Sonic hedgehog in the chick spinal cord.
2004,
Pubmed
Amato,
Hedgehog signaling in vertebrate eye development: a growing puzzle.
2004,
Pubmed
Barnes,
Patched1 interacts with cyclin B1 to regulate cell cycle progression.
2001,
Pubmed
,
Xenbase
Belecky-Adams,
Pax-6, Prox 1, and Chx10 homeobox gene expression correlates with phenotypic fate of retinal precursor cells.
1997,
Pubmed
Briscoe,
A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube.
2000,
Pubmed
Cayuso,
The Sonic hedgehog pathway independently controls the patterning, proliferation and survival of neuroepithelial cells by regulating Gli activity.
2006,
Pubmed
Coulombre,
Influence of mouse neural retina on regeneration of chick neural retina from chick embryonic pigmented epithelium.
1970,
Pubmed
Coulombre,
Regeneration of neural retina from the pigmented epithelium in the chick embryo.
1965,
Pubmed
Dahmane,
Sonic hedgehog regulates the growth and patterning of the cerebellum.
1999,
Pubmed
,
Xenbase
Das,
Identification of c-Kit receptor as a regulator of adult neural stem cells in the mammalian eye: interactions with Notch signaling.
2004,
Pubmed
Del Rio-Tsonis,
Eye regeneration at the molecular age.
2003,
Pubmed
,
Xenbase
Désiré,
Endogenous and exogenous fibroblast growth factor 2 support survival of chick retinal neurons by control of neuronal neuronal bcl-x(L) and bcl-2 expression through a fibroblast berowth factor receptor 1- and ERK-dependent pathway.
2000,
Pubmed
Ericson,
Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity.
1996,
Pubmed
Ericson,
Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling.
1997,
Pubmed
,
Xenbase
Fischer,
Exogenous growth factors induce the production of ganglion cells at the retinal margin.
2002,
Pubmed
Fischer,
Identification of a proliferating marginal zone of retinal progenitors in postnatal chickens.
2000,
Pubmed
Fischer,
Growth factors induce neurogenesis in the ciliary body.
2003,
Pubmed
Fuhrmann,
Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick.
2000,
Pubmed
Galy,
Activated MAPK/ERK kinase (MEK-1) induces transdifferentiation of pigmented epithelium into neural retina.
2002,
Pubmed
Haynes,
Retina repair, stem cells and beyond.
2004,
Pubmed
Hitchcock,
Persistent and injury-induced neurogenesis in the vertebrate retina.
2004,
Pubmed
Itoh,
Evolution of the Fgf and Fgfr gene families.
2004,
Pubmed
Jacob,
Gli proteins and the control of spinal-cord patterning.
2003,
Pubmed
Kenney,
Sonic hedgehog promotes G(1) cyclin expression and sustained cell cycle progression in mammalian neuronal precursors.
2000,
Pubmed
Kenney,
Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors.
2003,
Pubmed
Kubo,
Wnt2b inhibits differentiation of retinal progenitor cells in the absence of Notch activity by downregulating the expression of proneural genes.
2005,
Pubmed
Kubo,
Wnt2b controls retinal cell differentiation at the ciliary marginal zone.
2003,
Pubmed
Li,
Basic fibroblast growth factor exhibits dual and rapid regulation of cyclin D1 and p27 to stimulate proliferation of rat cerebral cortical precursors.
2004,
Pubmed
Liu,
Characterization of Wnt signaling components and activation of the Wnt canonical pathway in the murine retina.
2003,
Pubmed
Lobjois,
Specific regulation of cyclins D1 and D2 by FGF and Shh signaling coordinates cell cycle progression, patterning, and differentiation during early steps of spinal cord development.
2004,
Pubmed
Machold,
Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches.
2003,
Pubmed
Miyake,
Fgf19 regulated by Hh signaling is required for zebrafish forebrain development.
2005,
Pubmed
Mohammadi,
Structural basis for fibroblast growth factor receptor activation.
2005,
Pubmed
Moshiri,
Sonic hedgehog regulates proliferation of the retinal ciliary marginal zone in posthatch chicks.
2005,
Pubmed
Moshiri,
Retinal stem cells and regeneration.
2004,
Pubmed
Moshiri,
Persistent progenitors at the retinal margin of ptc+/- mice.
2004,
Pubmed
Oliver,
Transcriptional profiling of the Sonic hedgehog response: a critical role for N-myc in proliferation of neuronal precursors.
2003,
Pubmed
Osawa,
Sonic hedgehog stimulates the proliferation of rat gastric mucosal cells through ERK activation by elevating intracellular calcium concentration.
2006,
Pubmed
Palma,
Hedgehog-GLI signaling regulates the behavior of cells with stem cell properties in the developing neocortex.
2004,
Pubmed
Palma,
Sonic hedgehog controls stem cell behavior in the postnatal and adult brain.
2005,
Pubmed
Papaconstantinou,
Mercury, cadmium, and arsenite enhance heat shock protein synthesis in chick embryos prior to embryotoxicity.
2003,
Pubmed
Park,
Basic fibroblast growth factor induces retinal regeneration in vivo.
1989,
Pubmed
Park,
Induction of retinal regeneration in vivo by growth factors.
1991,
Pubmed
Perron,
The genetic sequence of retinal development in the ciliary margin of the Xenopus eye.
1998,
Pubmed
,
Xenbase
Pfaffl,
A new mathematical model for relative quantification in real-time RT-PCR.
2001,
Pubmed
Qualtrough,
Hedgehog signalling in colorectal tumour cells: induction of apoptosis with cyclopamine treatment.
2004,
Pubmed
Ríos-Muñoz,
Fibroblast growth factor 2 applied to the optic nerve after axotomy increases Bcl-2 and decreases Bax in ganglion cells by activating the extracellular signal-regulated kinase signaling pathway.
2005,
Pubmed
Romer,
Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/-)p53(-/-) mice.
2004,
Pubmed
Ruiz i Altaba,
The emergent design of the neural tube: prepattern, SHH morphogen and GLI code.
2003,
Pubmed
Saitsu,
Expression of the mouse Fgf15 gene is directly initiated by Sonic hedgehog signaling in the diencephalon and midbrain.
2005,
Pubmed
Sanchez,
In vivo inhibition of endogenous brain tumors through systemic interference of Hedgehog signaling in mice.
2005,
Pubmed
Sanchez,
Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling.
2004,
Pubmed
Schnapp,
Hedgehog signaling controls dorsoventral patterning, blastema cell proliferation and cartilage induction during axolotl tail regeneration.
2005,
Pubmed
Spence,
The hedgehog pathway is a modulator of retina regeneration.
2004,
Pubmed
Stenkamp,
Embryonic retinal gene expression in sonic-you mutant zebrafish.
2002,
Pubmed
Takenaka,
Regulation of chicken Hsp70 and Hsp90 family gene expression by transforming growth factor-beta 1.
1993,
Pubmed
Tsonis,
Lens and retina regeneration: transdifferentiation, stem cells and clinical applications.
2004,
Pubmed
Tsonis,
A novel role of the hedgehog pathway in lens regeneration.
2004,
Pubmed
Venkateswaran,
Production of anti-fibroblast growth factor receptor monoclonal antibodies by in vitro immunization.
1992,
Pubmed
Vergara,
CNS regeneration: a morphogen's tale.
2005,
Pubmed
Wallace,
Purkinje-cell-derived Sonic hedgehog regulates granule neuron precursor cell proliferation in the developing mouse cerebellum.
1999,
Pubmed
Wang,
Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina.
2005,
Pubmed
Wechsler-Reya,
Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog.
1999,
Pubmed
Weinstein,
FGFR-3 and FGFR-4 function cooperatively to direct alveogenesis in the murine lung.
1998,
Pubmed
Willbold,
A Hidden Retinal Regenerative Capacity from the Chick Ciliary Margin is Reactivated In Vitro, that is Accompanied by Down-regulation of Butyrylcholinesterase.
1992,
Pubmed
Xie,
A role of PDGFRalpha in basal cell carcinoma proliferation.
2001,
Pubmed
Xu,
Sonic hedgehog maintains the identity of cortical interneuron progenitors in the ventral telencephalon.
2005,
Pubmed
Yu,
Direct and indirect effects of hedgehog pathway activation in the mammalian retina.
2006,
Pubmed
Zhao,
BMP signaling is required for development of the ciliary body.
2002,
Pubmed
,
Xenbase
