Strict regulation of c-Raf kinase levels is required for early organogenesis of the vertebrate inner ear View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999-01

AUTHORS

Carmen Sanz, Yolanda León, Jakob Troppmair, Ulf R Rapp, Isabel Varela-Nieto

ABSTRACT

Regulation of organogenesis involves a dynamic balance of the mechanisms regulating cell division, differentiation and death. Here we have investigated the pattern of expression of c-Raf kinase in the inner ear during early developmental stages and the consequences of manipulating c-Raf levels by misexpression of c-raf viral vectors in organotypic cultures of otic vesicle explants. We found that otic vesicles expressed c-Raf and its level remained constant during embryonic days 2 and 3 (E2-E3). c-Raf activity was increased in response to insulin like growth factor-I (IGF-I) and the activation by IGF-I of the c-Raf kinase pathway was a requirement to turn on cell proliferation in the otic vesicle. Overexpression of c-raf in E2.5 explants increased the proliferative response to low serum and IGF-I and blocked differentiation induced by retinoic acid. The increase in c-Raf levels also prevented nerve growth factor (NGF)-dependent induction of programmed cell death. Consistent with these results, the expression of a dominant negative c-Raf mutant potentiated retinoic acid action and decreased the rate of cell proliferation. We conclude that a strict control of c-Raf levels is essential for the co-ordination of the biological processes that operate simultaneously during early inner ear development. More... »

PAGES

429

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1202312

DOI

http://dx.doi.org/10.1038/sj.onc.1202312

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/9927199


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