A role for the fibroblast growth factor receptor in cell fate decisions in the developing vertebrate retina.
The mature vertebrate retina contains seven major cell types that develop from an apparently homogenous population of precursor cells. Clonal analyses have suggested that environmental influences play a major role in specifying retinal cell identity. Fibroblast growth factor-2 is present in the developing retina and regulates the survival, proliferation and differentiation of developing retinal cells in culture. Here we have tested whether fibroblast growth factor receptor signaling biases retinal cell fate decisions in vivo. Fibroblast growth factor receptors were inhibited in retinal precursors in Xenopus embryos by expressing a dominant negative form of the receptor, XFD. Dorsal animal blastomeres that give rise to the retina were injected with cDNA expression constructs for XFD and a control non-functional mutant receptor, D48, and the cell fates of transgene-expressing cells in the mature retina determined. Fibroblast growth factor receptor blockade results in almost a 50% loss of photoreceptors and amacrine cells, and a concurrent 3.5-fold increase in Müller glia, suggesting a shift towards a Müller cell fate in the absence of a fibroblast growth factor receptor signal. Inhibition of non-fibroblast-growth-factor-mediated receptor signaling with a third mutant receptor, HAVO, alters cell fate in an opposite manner. These results suggest that it is the balance of fibroblast growth factor and non-fibroblast growth factor ligand signals that influences retinal cell genesis.
McFarlane
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Department of Cell Biology and Anatomy, Neuroscience Research Group, HMRB Room 171, University of Calgary, Calgary, Alberta, Canada, T2N 4N1. smcfarla@acs.ucalgary.ca.
Zuber
M E
ME
Holt
C E
CE
D000818:Animals; D001757:Blastomeres / Q000166:cytology; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D019281:Dimerization; D005346:Fibroblast Growth Factors / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008024:Ligands; D009457:Neuroglia / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology* / Q000378:metabolism; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D014982:Xenopus laevis / Q000196:embryology
D008024:Ligands; D016372:RNA, Antisense; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors