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Title: Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures

Canonical Wnt signaling triggers the formation of heterodimeric transcription factor complexes consisting of {beta}-catenin and T cell factors, and thereby controls the execution of specific genetic programs. During the expansion and neurogenic phases of embryonic neural development canonical Wnt signaling initially controls proliferation of neural progenitor cells, and later neuronal differentiation. Whether Wnt growth factors affect neural progenitor cells postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling on neural progenitors isolated from cerebral cortices of newborn mice. Expression profiling of pathway components revealed that these cells are fully equipped to respond to Wnt signals. However, Wnt pathway activation affected only a subset of neonatal progenitors and elicited a limited increase in proliferation and neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway activation only transiently stimulated S-phase entry but did not support long-term proliferation of progenitor cultures. The dampened nature of the Wnt response correlates with the predominant expression of inhibitory pathway components and the rapid actuation of negative feedback mechanisms. Interestingly, in differentiating cell cultures activation of canonical Wnt signaling reduced Hes1 and Hes5 expression suggesting that during postnatal neural development, Wnt/{beta}-catenin signaling enhances neurogenesis from progenitor cells by interfering with Notch pathwaymore » activity.« less
Authors:
 [1] ;  [1] ;  [1] ;  [2]
  1. Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg Stefan-Meier-Str. 17, D-79104 Freiburg (Germany)
  2. Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg Stefan-Meier-Str. 17, D-79104 Freiburg (Germany). E-mail: andreas.hecht@mol-med.uni-freiburg.de
Publication Date:
OSTI Identifier:
20972113
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 313; Journal Issue: 3; Other Information: DOI: 10.1016/j.yexcr.2006.11.002; PII: S0014-4827(06)00457-5; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL CULTURES; CELL DIFFERENTIATION; CELL PROLIFERATION; GROWTH FACTORS; INFANTS; MICE; STEM CELLS; TRANSCRIPTION FACTORS