TGFβ and FGF promote tendon progenitor fate and act downstream of muscle contraction to regulate tendon differentiation during chick limb development.
The molecular programme underlying tendon development has not been fully identified. Interactions with components of the musculoskeletal system are important for limb tendon formation. Limb tendons initiate their development independently of muscles; however, muscles are required for further tendon differentiation. We show that both FGF/ERK MAPK and TGFβ/SMAD2/3 signalling pathways are required and sufficient for SCX expression in chick undifferentiated limb cells, whereas the FGF/ERK MAPK pathway inhibits Scx expression in mouse undifferentiated limb mesodermal cells. During differentiation, muscle contraction is required to maintain SCX, TNMD and THBS2 expression in chick limbs. The activities of FGF/ERK MAPK and TGFβ/SMAD2/3 signalling pathways are decreased in tendons under immobilisation conditions. Application of FGF4 or TGFβ2 ligands prevents SCX downregulation in immobilised limbs. TGFβ2 but not FGF4 prevent TNMD and THBS2 downregulation under immobilisation conditions. We did not identify any intracellular crosstalk between both signalling pathways in their positive effect on SCX expression. Independently of each other, both FGF and TGFβ promote tendon commitment of limb mesodermal cells and act downstream of mechanical forces to regulate tendon differentiation during chick limb development.
Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7622, Inserm U1156, IBPS-Developmental Biology Laboratory, Paris F-75005, France.
Emmanuelle
E
Havis
Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7622, Inserm U1156, IBPS-Developmental Biology Laboratory, Paris F-75005, France.
Marie-Ange
MA
Bonnin
Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7622, Inserm U1156, IBPS-Developmental Biology Laboratory, Paris F-75005, France.
Joana
J
Esteves de Lima
Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7622, Inserm U1156, IBPS-Developmental Biology Laboratory, Paris F-75005, France.
Benjamin
B
Charvet
Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7622, Inserm U1156, IBPS-Developmental Biology Laboratory, Paris F-75005, France.
Cécile
C
Milet
Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7622, Inserm U1156, IBPS-Developmental Biology Laboratory, Paris F-75005, France delphine.duprez@upmc.fr.
Delphine
0000-0003-0248-7417
D
Duprez
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002642:Chick Embryo; D005121:Extremities / Q000196:embryology*; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D051379:Mice; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013710:Tendons / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors
Chick; Limb; Mechanobiology; Scleraxis; Tendon