Activated MAPK/ERK kinase (MEK-1) induces transdifferentiation of pigmented epithelium into neural retina.
During vertebrate eye development, the optic vesicle originating from the neuroectoderm is partitioned into a domain that will give rise to the neural retina (NR) and another that will give rise to the retinal pigmented epithelium (RPE). Previous studies have shown that ectopic expression of FGFs in the RPE induces RPE-to-NR transdifferentiation. Similarly, a naturally occurring mutation of the transcription factor Mitf in mouse resulted in the formation of a second neural retina in place of the dorsal RPE, but the putative signaling pathway linking FGF to Mitf regulation is presently unknown. In cultures of neural crest-derived melanocytes, the MAPK pathway was recently shown to target the Mitf transcription factor for ubiquitin-dependent proteolysis, resulting in a rapid degradation and downregulation. In the present study, we show that ectopic expression of a constitutively activated allele of MEK-1, the immediate upstream activator of the MAPK ERK, in chicken embryonic retina in ovo, induces transdifferentiation of the RPE into a neural-like epithelium that is correlated with a downregulation of Mitf expression in the presumptive RPE.
Galy
Anne
A
CNRS UMR 146, Institut Curie, Centre Universitaire, Laboratoire 110, 91405 Orsay Cedex, France.
Néron
Bertrand
B
Planque
Nathalie
N
Saule
Simon
S
Eychène
Alain
A
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005822:Genetic Vectors / Q000235:genetics; D048369:MAP Kinase Kinase 1; D051739:Microphthalmia-Associated Transcription Factor; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000196:embryology* / Q000201:enzymology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology* / Q000196:embryology* / Q000201:enzymology / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D051739:Microphthalmia-Associated Transcription Factor; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases