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

Sabine Fuhrmann, Amy N. Riesenberg, Amber M. Mathiesen, Erinn C. Brown, Monica L. Vetter, Nadean L Brown

Research output: Contribution to journalArticle

29 Citations (Scopus)

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/β-catenin pathway; however, the requirement for Wnt/β-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/β-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/β-catenin signaling. Reporter expression was also examined in embryos with a retina-specific deletion of the β-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 β-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/β-catenin signaling, pointing to an alternate role for this transcription factor family during retinal development.

Original languageEnglish (US)
Pages (from-to)432-440
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

Fingerprint

TCF Transcription Factors
Catenins
Retina
Transcription Factors
Population
Embryonic Structures
Cyclin-Dependent Kinase Inhibitor p27
Basic Helix-Loop-Helix Transcription Factors
Amacrine Cells
Cell Cycle Proteins
Wnt Signaling Pathway
Gene Deletion
Ganglia
Transgenic Mice
Stem Cells
Immunohistochemistry
T-Lymphocytes
Messenger RNA

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Characterization of a transient TCF/LEF-responsive progenitor population in the embryonic mouse retina. / Fuhrmann, Sabine; Riesenberg, Amy N.; Mathiesen, Amber M.; Brown, Erinn C.; Vetter, Monica L.; Brown, Nadean L.

In: Investigative Ophthalmology and Visual Science, Vol. 50, No. 1, 01.2009, p. 432-440.

Research output: Contribution to journalArticle

Fuhrmann, Sabine ; Riesenberg, Amy N. ; Mathiesen, Amber M. ; Brown, Erinn C. ; Vetter, Monica L. ; Brown, Nadean L. / Characterization of a transient TCF/LEF-responsive progenitor population in the embryonic mouse retina. In: Investigative Ophthalmology and Visual Science. 2009 ; Vol. 50, No. 1. pp. 432-440.
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