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Differential, age‐dependent MEK‐ERK and PI3K‐Akt activation by insulin acting as a survival factor during embryonic retinal development
Author(s) -
Chavarría Teresa,
Valenciano Ana I.,
Mayordomo Raquel,
Egea Joaquim,
Comella Joan X.,
Hallböök Finn,
de Pablo Flora,
de la Rosa Enrique J.
Publication year - 2007
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.20554
Subject(s) - biology , neuroepithelial cell , microbiology and biotechnology , pi3k/akt/mtor pathway , mapk/erk pathway , programmed cell death , protein kinase b , embryonic stem cell , growth factor , retina , neuroscience , neural stem cell , apoptosis , kinase , signal transduction , stem cell , receptor , genetics , gene
Programmed cell death is a genuine developmental process of the nervous system, affecting not only projecting neurons but also proliferative neuroepithelial cells and young neuroblasts. The embryonic chick retina has been employed to correlate in vivo and in vitro studies on cell death regulation. We characterize here the role of two major signaling pathways, PI3K‐Akt and MEK‐ERK, in controlled retinal organotypic cultures from embryonic day 5 (E5) and E9, when cell death preferentially affects proliferating neuroepithelial cells and ganglion cell neurons, respectively. The relative density of programmed cell death in vivo was much higher in the proliferative and early neurogenic stages of retinal development (E3–E5) than during neuronal maturation and synaptogenesis (E8–E19). In organotypic cultures from E5 and E9 retinas, insulin, as the only growth factor added, was able to completely prevent cell death induced by growth factor deprivation. Insulin activated both the PI3K‐Akt and the MEK‐ERK pathways. Insulin survival effect, however, was differentially blocked at the two stages. At E5, the effect was blocked by MEK inhibitors, whereas at E9 it was blocked by PI3K inhibitors. The cells which were found to be dependent on insulin activation of the MEK‐ERK pathway at E5 were mostly proliferative neuroepithelial cells. These observations support a remarkable specificity in the regulation of early neural cell death. © 2007 Wiley Periodicals, Inc. Develop Neurobiol 67:1777–1788, 2007