Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes

Item Type:	Article
Title:	Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes
Creators Name:	Hill, T.P. and Spaeter, D. and Taketo, M.M. and Birchmeier, W. and Hartmann, C.
Abstract:	Osteoblasts and chondrocytes are involved in building up the vertebrate skeleton and are thought to differentiate from a common mesenchymal precursor, the osteo-chondroprogenitor. Although numerous transcription factors involved in chondrocyte and osteoblast differentiation have been identified, little is known about the signals controlling lineage decisions of the two cell types. Here, we show by conditionally deleting beta-catenin in limb and head mesenchyme that beta-catenin is required for osteoblast lineage differentiation. Osteoblast precursors lacking beta-catenin are blocked in differentiation and develop into chondrocytes instead. In vitro experiments demonstrate that this is a cell-autonomous function of beta-catenin in an osteoblast precursor. Furthermore, detailed in vivo and in vitro loss- and gain-of-function analyses reveal that beta-catenin activity is necessary and sufficient to repress the differentiation of mesenchymal cells into Runx2- and Sox9-positive skeletal precursors. Thus, canonical Wnt/beta-catenin signaling is essential for skeletal lineage differentiation, preventing transdifferentiation of osteoblastic cells into chondrocytes.
Keywords:	Cell Differentiation, Chondrocytes, Chondrogenesis, Core Binding Factor Alpha 1 Subunit, Cytoskeletal Proteins, DNA-Binding Proteins, Developmental Gene Expression Regulation, High Mobility Group Proteins, Intercellular Signaling Peptides and Proteins, Mesoderm, Osteoblasts, Osteogenesis, SOX9 Transcription Factor, Signal Transduction, Trans-Activators, Transcription Factor AP-2, Transcription Factors, Wnt Proteins, beta Catenin, Animals, Mice
Source:	Developmental Cell
ISSN:	1534-5807
Publisher:	Cell Press
Volume:	8
Number:	5
Page Range:	727-738
Date:	1 May 2005
Official Publication:	https://doi.org/10.1016/j.devcel.2005.02.013
PubMed:	View item in PubMed

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