Spry1 and Spry2 are necessary for lens vesicle separation and corneal differentiation.
Invest Ophthalmol Vis Sci
; 52(9): 6887-97, 2011 Aug 29.
Article
en En
| MEDLINE
| ID: mdl-21743007
PURPOSE: The studies reported here were performed to analyze the roles of Sproutys (Sprys), downstream targets and negative feedback regulators of the fibroblast growth factor (FGF) signaling pathway, in lens and corneal differentiation. METHODS: Spry1 and -2 were conditionally deleted in the lens and corneal epithelial precursors using the Le-Cre transgene and floxed alleles of Spry1 and -2. Alterations in lens and corneal development were assessed by hematoxylin and eosin staining, in situ hybridization, and immunohistochemistry. RESULTS: Spry1 and -2 were upregulated in the lens fibers at the onset of fiber differentiation. FGF signaling was both necessary and sufficient for induction of Spry1 and -2 in the lens fiber cells. Spry1 and -2 single- or double-null lenses failed to separate from the overlying ectoderm and showed persistent keratolenticular stalks. Apoptosis of stalk cells, normally seen during lens vesicle detachment from the ectoderm, was inhibited in Spry mutant lenses, with concomitant ERK activation. Prox1 and p57(KIP2), normally upregulated at the onset of fiber differentiation were prematurely induced in the Spry mutant lens epithelial cells. However, terminal differentiation markers such as ß- or γ-crystallin were not induced. Corneal epithelial precursors in Spry1 and -2 double mutants showed increased proliferation with elevated expression of Erm and DUSP6 and decreased expression of the corneal differentiation marker K12. CONCLUSIONS: Collectively, the results indicate that Spry1 and -2 (1) through negative modulation of ERKs allow lens vesicle separation, (2) are targets of FGF signaling in the lens during initiation of fiber differentiation and (3) function redundantly in the corneal epithelial cells to suppress proliferation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
ADN
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Regulación del Desarrollo de la Expresión Génica
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Córnea
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Cristalino
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Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos