Transcriptomic analysis of mouse limb tendon cells during development
Havis, Emmanuelle; Bonnin, Marie-Ange; Olivera-Martinez, Isabel; Nazaret, Nicolas; Ruggiu, Mathilde; Weibel, Jennifer; Durand, Charles; Guerquin, Marie-Justine; Bonod-Bidaud, Christelle; Ruggiero, Florence; Schweitzer, Ronen; Duprez, Delphine
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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Journal articles; Life Sciences [q-bio]; Université Pierre et Marie Curie; Laboratoire de Biologie du Développement; Formation et réparation des muscles et des tendons; Migration et différenciation des cellules souches hématopoiétiques; C.elegans Hérédité et Développement; Institut de Biologie Paris Seine; Sorbonne Université; Faculté des Sciences de Sorbonne Université
ISSN: 0950-1991; EISSN: 1477-9129; Development (Cambridge, England); https://hal.archives-ouvertes.fr/hal-01538325; Development (Cambridge, England), Company of Biologists, 2014, 141 (19), pp.3683-3696. ⟨10.1242/dev.108654⟩