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J.–W. Jiao, S. Rezny, M. Takeda, X. Huang, D.F. Chen; FGF15 in Retinal Neurogenesis and Cell Fate Determination . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5755.
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The objective of this research plan is to study the role of FGF15 in retinal neurogenesis and cell fate determination in development. Uncovering the molecular basis that controls retinal development and neuron generation is important for our understanding of developmental diseases in the retina and may provide new avenues for treating retinal degeneration and disorders. Fibroblast growth factor (FGF) family proteins have emerged as important players mediating neural induction and differentiation and progenitor cell specification in the developing central nervous system (CNS). FGF15 is a novel member of the FGF family, which expression is region specific in development Expression of FGF15 first appears between E7.5 and E8.0 in the mouse brain, reaches a high level thereafter, but becomes undetectable in the adult. The retina is an excellent model system for the study of neural development in the CNS.
Pattern of FGF15 expression in the retina was determined using cDNA microarray and confirmed by RT–PCR and in situ hybridization.. Neural progenitor cells isolated from embryonic mouse retina were plated in 4–well chamber slides at a density of 55,000–75,000 cells/well. Cells were maintained in a media containing 1% fetal bovine serum for 6 days. Immunohistochemistry was used to determine progenitor cell differentiation and cell fates.
Expression of FGF15 commences at E12 in the mouse retina, peaks around E14–E16, and is downregulated drastically after E18, coincided with the end of early retinogenesis or initiation of late–born neurogenesis. Addition of FGF15 to retinal progenitor cell cultures promoted the differentiation of early born neurons–retinal ganglion cells.
The data suggest that FGF15 plays an important role in the regulation of retinal neurogenesis by signaling retinal progenitor cells to generate early–born neurons. This study may provide insight into the molecular pathways controlling retinogenesis and lead to new therapeutic strategies for retinal degeneration.
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