title: Expression of Hoxa2 in cells entering chondrogenesis impairs overall cartilage development.
abstract: Vertebrate Hox genes act as developmental architects by patterning embryonic structures like axial skeletal elements, limbs, brainstem territories, or neural crest derivatives. While active during the patterning steps of development, these genes turn out to be down-regulated in specific differentiation programs like that leading to chondrogenesis. To investigate why chondrocyte differentiation is correlated to the silencing of a Hox gene, we generated transgenic mice allowing Cre-mediated conditional misexpression of Hoxa2 and induced this gene in Collagen 2 alpha 1-expressing cells committed to enter chondrogenesis. Persistent Hoxa2 expression in chondrogenic cells resulted in overall chondrodysplasia with delayed cartilage hypertrophy, mineralization, and ossification but without proliferation defects. The absence of skeletal patterning anomaly and the regular migration of precursor cells indicated that the condensation step of chondrogenesis was normal. In contrast, closer examination at the differentiation step showed severely impaired chondrocyte differentiation. In addition, this inhibition affected structures independently of their embryonic origin. In conclusion, for the first time here, by a cell-type specific misexpression, we precisely uncoupled the patterning function of Hoxa2 from its involvement in regulating differentiation programs per se and demonstrate that Hoxa2 displays an anti-chondrogenic activity that is distinct from its patterning function.
authors.affiliation: Developmental Genetics Unit, Université catholique de Louvain, Brussels, Belgium. rezsohazy@vete.ucl.ac.be
authors.forename: Laurent
authors.initials: L
authors.lastname: Massip
authors.forename: Fabien
authors.initials: F
authors.lastname: Ectors
authors.forename: Pierre
authors.initials: P
authors.lastname: Deprez
authors.forename: Mehdi
authors.initials: M
authors.lastname: Maleki
authors.forename: Catherine
authors.initials: C
authors.lastname: Behets
authors.forename: Benoît
authors.initials: B
authors.lastname: Lengelé
authors.forename: Philippe
authors.initials: P
authors.lastname: Delahaut
authors.forename: Jacques
authors.initials: J
authors.lastname: Picard
authors.forename: René
authors.initials: R
authors.lastname: Rezsöhazy
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002356:Cartilage / Q000196:embryology* / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D020219:Chondrogenesis / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D010012:Osteogenesis
chemical_list: C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D018398:Homeodomain Proteins; C489833:Hoxa2 protein, mouse