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Patched 1 is a crucial determinant of asymmetry and digit number in the vertebrate limb.
Butterfield, Natalie C; Metzis, Vicki; McGlinn, Edwina; Bruce, Stephen J; Wainwright, Brandon J; Wicking, Carol.
Afiliação
  • Butterfield NC; The University of Queensland, Institute for Molecular Bioscience, Queensland, Australia.
Development ; 136(20): 3515-24, 2009 Oct.
Article em En | MEDLINE | ID: mdl-19783740
ABSTRACT
The vertebrate hedgehog receptor patched 1 (Ptc1) is crucial for negative regulation of the sonic hedgehog (Shh) pathway during anterior-posterior patterning of the limb. We have conditionally inactivated Ptc1 in the mesenchyme of the mouse limb using Prx1-Cre. This results in constitutive activation of hedgehog (Hh) signalling during the early stages of limb budding. Our data suggest that variations in the timing and efficiency of Cre-mediated excision result in differential forelimb and hindlimb phenotypes. Hindlimbs display polydactyly (gain of digits) and a molecular profile similar to the Gli3 mutant extra-toes. Strikingly, forelimbs are predominantly oligodactylous (displaying a loss of digits), with a symmetrical, mirror-image molecular profile that is consistent with re-specification of the anterior forelimb to a posterior identity. Our data suggest that this is related to very early inactivation of Ptc1 in the forelimb perturbing the gene regulatory networks responsible for both the pre-patterning and the subsequent patterning stages of limb development. These results establish the importance of the downstream consequences of Hh pathway repression, and identify Ptc1 as a key player in limb patterning even prior to the onset of Shh expression.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Superfície Celular / Regulação da Expressão Gênica no Desenvolvimento / Padronização Corporal / Extremidades Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Development Assunto da revista: BIOLOGIA / EMBRIOLOGIA Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Austrália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Superfície Celular / Regulação da Expressão Gênica no Desenvolvimento / Padronização Corporal / Extremidades Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Development Assunto da revista: BIOLOGIA / EMBRIOLOGIA Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Austrália