Characterization of a transient TCF/LEF-responsive progenitor population in the embryonic mouse retina.

Fuhrmann S, Riesenberg AN, Mathiesen AM, Brown EC, Vetter ML, Brown NL
Invest Ophthalmol Vis Sci. 2009 50 (1): 432-40

PMID: 18599572 · PMCID: PMC2615067 · DOI:10.1167/iovs.08-2270

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.

MeSH Terms (16)

Animals Axin Protein Basic Helix-Loop-Helix Transcription Factors beta Catenin Cell Count Cell Cycle Proteins Cytoskeletal Proteins Embryonic Stem Cells Fluorescent Antibody Technique, Indirect In Situ Hybridization Mice Mice, Transgenic Retina RNA, Messenger TCF Transcription Factors Wnt Proteins

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