Long bone development requires a threshold of Hox function.
Dev Biol
; 392(2): 454-65, 2014 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-24930703
ABSTRACT
The Hoxd(Del(11-13)) mutant is one of the animal models for human synpolydactyly, characterized by short and syndactylous digits. Here we have characterized in detail the cartilage and bone defects in these mutants. We report two distinct phenotypes (i) a delay and change in pattern of chondrocyte maturation of metacarpals/metatarsals and (ii) formation of a poor and not centrally positioned primary ossification center in the proximal-intermediate phalanx. In the metacarpals of Hoxd(Del(11-13)) mutants, ossification occurs postnataly, in the absence of significant Ihh expression and without the establishment of growth plates, following patterns similar to those of short bones. The strong downregulation in Ihh expression is associated with a corresponding increase of the repressor form of Gli3. To evaluate the contribution of this alteration to the phenotype, we generated double Hoxd(Del(11-13));Gli3 homozygous mutants. Intriguingly, these double mutants showed a complete rescue of the phenotype in metatarsals but only partial phenotypic rescue in metacarpals. Our results support Hox genes being required in a dose-dependent manner for long bone cartilage maturation and suggest that and excess of Gli3R mediates a significant part of the Hoxd(Del(11-13)) chondrogenic phenotype.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenvolvimento Ósseo
/
Sindactilia
/
Proteínas de Homeodomínio
/
Regulação da Expressão Gênica no Desenvolvimento
/
Modelos Animais de Doenças
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Dev Biol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Espanha