title: Transcriptomic analysis of mouse limb tendon cells during development.
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.
authors.affiliation: CNRS UMR 7622, IBPS-Developmental Biology Laboratory, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, IBPS-Developmental Biology Laboratory, Paris F-75005, France Inserm U1156, Paris F-75005, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Havis
authors.affiliation: CNRS UMR 7622, IBPS-Developmental Biology Laboratory, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, IBPS-Developmental Biology Laboratory, Paris F-75005, France Inserm U1156, Paris F-75005, France.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Bonnin
authors.affiliation: CNRS UMR 7622, IBPS-Developmental Biology Laboratory, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, IBPS-Developmental Biology Laboratory, Paris F-75005, France.
authors.forename: Isabel
authors.initials: I
authors.lastname: Olivera-Martinez
authors.affiliation: ProfileXpert, SFR Lyon-Est, UMS 3453 CNRS/US7 INSERM, Lyon F-69008, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nazaret
authors.affiliation: CNRS UMR 7622, IBPS-Developmental Biology Laboratory, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, IBPS-Developmental Biology Laboratory, Paris F-75005, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Ruggiu
authors.affiliation: Research Division, Shriners Hospital for Children, Portland, OR 97239, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Weibel
authors.affiliation: CNRS UMR 7622, IBPS-Developmental Biology Laboratory, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, IBPS-Developmental Biology Laboratory, Paris F-75005, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Durand
authors.affiliation: CNRS UMR 7622, IBPS-Developmental Biology Laboratory, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, IBPS-Developmental Biology Laboratory, Paris F-75005, France.
authors.forename: Marie-Justine
authors.initials: MJ
authors.lastname: Guerquin
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université Lyon 1, CNRS UMR5242, Ecole Normale Supérieure de Lyon, Lyon F-69007, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Bonod-Bidaud
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université Lyon 1, CNRS UMR5242, Ecole Normale Supérieure de Lyon, Lyon F-69007, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Ruggiero
authors.affiliation: Research Division, Shriners Hospital for Children, Portland, OR 97239, USA.
authors.forename: Ronen
authors.initials: R
authors.lastname: Schweitzer
authors.affiliation: CNRS UMR 7622, IBPS-Developmental Biology Laboratory, Paris F-75005, France Sorbonne Universités, UPMC Univ Paris 06, IBPS-Developmental Biology Laboratory, Paris F-75005, France Inserm U1156, Paris F-75005, France delphine.duprez@upmc.fr.
authors.forename: Delphine
authors.initials: D
authors.lastname: Duprez
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D019295:Computational Biology; D005121:Extremities / Q000502:physiology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D046228:Microarray Analysis; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013710:Tendons / Q000166:cytology* / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D020928:Mitogen-Activated Protein Kinases; D016212:Transforming Growth Factor beta; C503815:Scx protein, mouse
keywords: ERK; Limb; Mouse; SMAD2/3; Scleraxis; TGF-β; Tendon; Transcriptome