Characterization of a transient TCF/LEF-responsive progenitor population in the embryonic mouse retina.
Invest Ophthalmol Vis Sci
; 50(1): 432-40, 2009 Jan.
Article
em En
| MEDLINE
| ID: mdl-18599572
ABSTRACT
PURPOSE:
High mobility group (HMG) transcription factors of the T-cell-specific transcription factor/lymphoid enhancer binding factor (TCF/LEF) family are a class of intrinsic regulators that are dynamically expressed in the embryonic mouse retina. Activation of TCF/LEFs is a hallmark of the Wnt/beta-catenin pathway; however, the requirement for Wnt/beta-catenin and noncanonical Wnt signaling during mammalian retinal development remains unclear. The goal of the study was to characterize more fully a TCF/LEF-responsive retinal progenitor population in the mouse embryo and to correlate this with Wnt/beta-catenin signaling.METHODS:
TCF/LEF activation was analyzed in the TOPgal (TCF optimal promoter) reporter mouse at embryonic ages and compared to Axin2 mRNA expression, an endogenous readout of Wnt/beta-catenin signaling. Reporter expression was also examined in embryos with a retina-specific deletion of the beta-catenin gene (Ctnnb1), using Six3-Cre transgenic mice. Finally, the extent to which TOPgal cells coexpress cell cycle proteins, basic helix-loop-helix (bHLH) transcription factors, and other retinal cell markers was tested by double immunohistochemistry.RESULTS:
TOPgal reporter activation occurred transiently in a subpopulation of embryonic retinal progenitor cells. Axin2 was not expressed in the central retina, and TOPgal reporter expression persisted in the absence of beta-catenin. Although a proportion of TOPgal-labeled cells were proliferative, most coexpressed the cyclin-dependent kinase inhibitor p27/Kip1.CONCLUSIONS:
TOPgal cells give rise to the four earliest cell types ganglion, amacrine, horizontal, and photoreceptor. TCF/LEF activation in the central retina does not correlate with Wnt/beta-catenin signaling, pointing to an alternate role for this transcription factor family during retinal development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Retina
/
Fatores de Transcrição TCF
/
Células-Tronco Embrionárias
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article