Transcriptomic analysis of mouse limb tendon cells during development.

Emmanuelle Havis, Marie-Ange Bonnin, Isabel Olivera-Martinez, Nicolas Nazaret, Mathilde Ruggiu, Jennifer Weibel, Charles Durand, Marie-Justine Guerquin, Christelle Bonod-Bidaud, Florence Ruggiero, Ronen Schweitzer, Delphine Duprez

Index: Development 141(19) , 3683-96, (2014)

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Abstract

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-β and MAPK. TGF-β/SMAD2/3 gain- and loss-of-function experiments in mouse limb explants and mesenchymal stem cells showed that TGF-β signalling was sufficient and required via SMAD2/3 to drive mouse mesodermal stem cells towards the tendon lineage ex vivo and in vitro. TGF-β 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.© 2014. Published by The Company of Biologists Ltd.