title: EGR1 and EGR2 involvement in vertebrate tendon differentiation.
abstract: The molecules involved in vertebrate tendon formation during development remain largely unknown. To date, only two DNA-binding proteins have been identified as being involved in vertebrate tendon formation, the basic helix-loop-helix transcription factor Scleraxis and, recently, the Mohawk homeobox gene. We investigated the involvement of the early growth response transcription factors Egr1 and Egr2 in vertebrate tendon formation. We established that Egr1 and Egr2 expression in tendon cells was correlated with the increase of collagen expression during tendon cell differentiation in embryonic limbs. Vertebrate tendon differentiation relies on a muscle-derived FGF (fibroblast growth factor) signal. FGF4 was able to activate the expression of Egr genes and that of the tendon-associated collagens in chick limbs. Egr gene misexpression experiments using the chick model allowed us to establish that either Egr gene has the ability to induce de novo expression of the reference tendon marker scleraxis, the main tendon collagen Col1a1, and other tendon-associated collagens Col3a1, Col5a1, Col12a1, and Col14a1. Mouse mutants for Egr1 or Egr2 displayed reduced amounts of Col1a1 transcripts and a decrease in the number of collagen fibrils in embryonic tendons. Moreover, EGR1 and EGR2 trans-activated the mouse Col1a1 proximal promoter and were recruited to the tendon regulatory regions of this promoter. These results identify EGRs as novel DNA-binding proteins involved in vertebrate tendon differentiation by regulating type I collagen production.
authors.affiliation: Université Pierre et Marie Curie, CNRS UMR 7622, Paris 75005, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Lejard
authors.forename: Frédéric
authors.initials: F
authors.lastname: Blais
authors.forename: Marie-Justine
authors.initials: MJ
authors.lastname: Guerquin
authors.forename: Aline
authors.initials: A
authors.lastname: Bonnet
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Bonnin
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Havis
authors.forename: Maryline
authors.initials: M
authors.lastname: Malbouyres
authors.forename: Christelle Bonod
authors.initials: CB
authors.lastname: Bidaud
authors.forename: Géraldine
authors.initials: G
authors.lastname: Maro
authors.forename: Pascale
authors.initials: P
authors.lastname: Gilardi-Hebenstreit
authors.forename: Jérome
authors.initials: J
authors.lastname: Rossert
authors.forename: Florence
authors.initials: F
authors.lastname: Ruggiero
authors.forename: Delphine
authors.initials: D
authors.lastname: Duprez
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000096:biosynthesis / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D002642:Chick Embryo; D002645:Chickens; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology*; D051519:Fibroblast Growth Factor 4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D013710:Tendons / Q000166:cytology / Q000196:embryology*
chemical_list: D030161:Avian Proteins; D051792:Basic Helix-Loop-Helix Proteins; D003094:Collagen; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D051519:Fibroblast Growth Factor 4; C486109:Egr1 protein, mouse; C497327:Egr2 protein, mouse; C496446:Fgf4 protein, mouse; C503821:SCX protein, Gallus gallus; C503815:Scx protein, mouse