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c-Raf regulates cell survival and retinal ganglion cell morphogenesis during neurogenesis

AuthorsPimentel, Belén; Sanz, Carmen; Varela-Nieto, Isabel ; Rapp, Ulf R.; Pablo, Flora de ; De la Rosa, Enrique J.
Cell death
Cell survival
Neural development
Retinal ganglion cell
Chick embryo
Issue Date1-May-2000
PublisherSociety for Neuroscience
CitationJournal of Neuroscience 20(9): 3254-3262 (2000)
AbstractThe signaling cascade Ras/Raf/mitogen-activated protein kinases modulates cell proliferation, differentiation, and survival, all key cellular processes during neural development. To better define the in vivo role of Raf during chick retinal neurogenesis, we interfered with Raf-dependent signaling during days 4.5 to 7.5 of embryonic development by expressing a dominant negative mutant of c-Raf (DeltaRaf), which blocks Ras-dependent Raf activation, and by overexpressing wild-type c-Raf. DeltaRaf expression induced an increase in cell death by apoptosis, whereas it did not affect overall cell proliferation and differentiation. In parallel, the number of Islet-1/2-positive and TUJ1-positive retinal ganglion cells were diminished in their definitive layer, whereas there was an increase in the number of mislocated Islet-1/2-positive cells. This disturbed morphogenesis correlated with a disruption of the optic fiber layer. Conversely, c-Raf overexpression caused moderate opposite effects on apoptosis. These results frame in vivo early neurogenesis processes in which c-Raf is essential.
Description9 pages, 6 figures.
Publisher version (URL)http://www.jneurosci.org/cgi/content/full/20/9/3254
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