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Glucocorticoid receptor antagonizes EGFR function to regulate eyelid development.

AuthorsSanchis, Ana ; Bayo, Pilar ; Sevilla, Lisa M. ; Pérez, Paloma
KeywordsGlucocorticoid receptor
Genetically modified mice
Epithelial cells
Eye development
Issue Date2010
PublisherUniversidad del País Vasco
CitationInternational Journal of Developmental Biology 54(10):1473-80 (2010)
AbstractThe glucocorticoid receptor (GR) plays a crucial role in epidermal morphogenesis during embryonic development, as demonstrated by analyzing genetically modified mouse models of GR gain- and loss-of-function. Eyelid formation constitutes a useful model to study epithelial development, as it requires coordinated regulation of keratinocyte proliferation, apoptosis and migration. We have analyzed this biological process in GR(-/-) embryos during ontogeny. Our data demonstrate that GR deficiency results in delayed and impaired eyelid closure, as illustrated by increased keratinocyte proliferation and apoptosis along with impaired differentiation in GR(-/-) eyelid epithelial cells. These defects are due, at least in part, to the lack of antagonism between GR and epidermal growth factor receptor (EGFR) signaling, causing sustained activation of the MAPK/AP-1 pathway and the upregulation of keratin K6 at embryonic stage E18.5. Additionally, we demonstrate that GR regulates epithelial cell migration in vitro by interfering with EGFR-mediated signaling. Overall, GR/EGFR antagonism appears as a major mechanism regulating ocular epithelial development.
Description8 páginas, 4 figuras
Publisher version (URL)http://dx.doi.org/10.1387/ijdb.103071as
Appears in Collections:(IBV) Artículos
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