期刊
DEVELOPMENT
卷 141, 期 19, 页码 3683-3696出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.108654
关键词
Transcriptome; Limb; Tendon; Mouse; Scieraxis; TGF-beta; SMAD2/3; ERK
资金
- Fondation pour la Recherche Medicale (FRM)
- Centre National de la Recherche Scientifique (CNRS)
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Universite Pierre et Marie Curie (UPMC)
- Agence Nationale de la Recherche (ANR)
- Association Francaise contre les Myopathies (AFM)
- FP6 NOE Myores
The molecular signals driving tendon development are not fully identified. We have undertaken a transcriptome analysis of mouse limb tendon cells that were isolated at different stages of development based on scleraxis ( Scx) expression. Microarray comparisons allowed us to establish a list of genes regulated in tendon cells during mouse limb development. Bioinformatics analysis of the tendon transcriptome showed that the two most strongly modified signalling pathways were TGF-beta and MAPK. TGF-beta/SMAD2/3 gain- and loss-of-function experiments in mouse limb explants and mesenchymal stem cells showed that TGF-beta signalling was sufficient and required via SMAD2/3 to drive mouse mesodermal stem cells towards the tendon lineage ex vivo and in vitro. TGF-beta was also sufficient for tendon gene expression in late limb explants during tendon differentiation. FGF does not have a tenogenic effect and the inhibition of the ERK MAPK signalling pathway was sufficient to activate Scx in mouse limb mesodermal progenitors and mesenchymal stem cells.
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