Open Access

Quantitative and kinetic profile of Wnt/β-catenin signaling components during human neural progenitor cell differentiation

  • Orianne Mazemondet1, 4,
  • Rayk Hubner1,
  • Jana Frahm1,
  • Dirk Koczan2,
  • Benjamin M. Bader3,
  • Dieter G. Weiss3,
  • Adelinde M. Uhrmacher4,
  • Moritz J. Frech1,
  • Arndt Rolfs1Email author and
  • Jiankai Luo1Email author
Cellular & Molecular Biology LettersAn International Journal201116:515

DOI: 10.2478/s11658-011-0021-0

Received: 22 March 2011

Accepted: 3 August 2011

Published: 29 July 2011

Abstract

ReNcell VM is an immortalized human neural progenitor cell line with the ability to differentiate in vitro into astrocytes and neurons, in which the Wnt/β-catenin pathway is known to be involved. However, little is known about kinetic changes of this pathway in human neural progenitor cell differentiation. In the present study, we provide a quantitative profile of Wnt/β-catenin pathway dynamics showing its spatio-temporal regulation during ReNcell VM cell differentiation. We show first that T-cell factor dependent transcription can be activated by stabilized β-catenin. Furthermore, endogenous Wnt ligands, pathway receptors and signaling molecules are temporally controlled, demonstrating changes related to differentiation stages. During the first three hours of differentiation the signaling molecules LRP6, Dvl2 and β-catenin are spatio-temporally regulated between distinct cellular compartments. From 24 h onward, components of the Wnt/β-catenin pathway are strongly activated and regulated as shown by mRNA up-regulation of Wnt ligands (Wnt5a and Wnt7a), receptors including Frizzled-2, -3, -6, -7, and -9, and co-receptors, and target genes including Axin2. This detailed temporal profile of the Wnt/β-catenin pathway is a first step to understand, control and to orientate, in vitro, human neural progenitor cell differentiation.

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