Pitx1 directly modulates the core limb development program to implement hindlimb identity.
Development
; 144(18): 3325-3335, 2017 09 15.
Article
em En
| MEDLINE
| ID: mdl-28807899
ABSTRACT
Forelimbs (FLs) and hindlimbs (HLs) develop complex musculoskeletal structures that rely on the deployment of a conserved developmental program. Pitx1, a transcription factor gene with expression restricted to HL and absent from FL, plays an important role in generating HL features. The genomic mechanisms by which Pitx1 effects HL identity remain poorly understood. Here, we use expression profiling and analysis of direct Pitx1 targets to characterize the HL- and FL-restricted genetic programs in mouse and situate the Pitx1-dependent gene network within the context of limb-specific gene regulation. We show that Pitx1 is a crucial component of a narrow network of HL-restricted regulators, acting on a developmental program that is shared between FL and HL. Pitx1 targets sites that are in a similar chromatin state in FL and HL and controls expression of patterning genes as well as the chondrogenic program, consistent with impaired chondrogenesis in Pitx1-/- HL. These findings support a model in which multifactorial actions of a limited number of HL regulators redirect the generic limb development program in order to generate the unique structural features of the limb.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Organogênese
/
Fatores de Transcrição Box Pareados
/
Membro Posterior
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article