RBPjkappa-dependent Notch signaling regulates mesenchymal progenitor cell proliferation and differentiation during skeletal development.
Development
; 137(9): 1461-71, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-20335360
ABSTRACT
The Notch pathway has recently been implicated in mesenchymal progenitor cell (MPC) differentiation from bone marrow-derived progenitors. However, whether Notch regulates MPC differentiation in an RBPjkappa-dependent manner, specifies a particular MPC cell fate, regulates MPC proliferation and differentiation during early skeletal development or controls specific Notch target genes to regulate these processes remains unclear. To determine the exact role and mode of action for the Notch pathway in MPCs during skeletal development, we analyzed tissue-specific loss-of-function (Prx1Cre; Rbpjk(f/f)), gain-of-function (Prx1Cre; Rosa-NICD(f/+)) and RBPjkappa-independent Notch gain-of-function (Prx1Cre; Rosa-NICD(f/+); Rbpjk(f/f)) mice for defects in MPC proliferation and differentiation. These data demonstrate for the first time that the RBPjkappa-dependent Notch signaling pathway is a crucial regulator of MPC proliferation and differentiation during skeletal development. Our study also implicates the Notch pathway as a general suppressor of MPC differentiation that does not bias lineage allocation. Finally, Hes1 was identified as an RBPjkappa-dependent Notch target gene important for MPC maintenance and the suppression of in vitro chondrogenesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osso e Ossos
/
Transdução de Sinais
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Diferenciação Celular
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Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina
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Receptores Notch
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Células-Tronco Mesenquimais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Development
Assunto da revista:
BIOLOGIA
/
EMBRIOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos