Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses.
Nat Neurosci
; 12(4): 409-17, 2009 Apr.
Article
em En
| MEDLINE
| ID: mdl-19287388
ABSTRACT
Sonic Hedgehog (Shh) has dual roles in vertebrate development, promoting progenitor cell proliferation and inducing tissue patterning. We found that the mitogenic and patterning functions of Shh can be uncoupled from one another. Using a genetic approach to selectively inhibit Shh-proteoglycan interactions in a mouse model, we found that binding of Shh to proteoglycans was required for proliferation of neural stem/precursor cells, but not for tissue patterning. Shh-proteoglycan interactions regulated both spatial and temporal features of Shh signaling. Proteoglycans localized Shh to specialized mitogenic niches and also acted at the single-cell level to regulate the duration of Shh signaling, thereby promoting a gene expression program that is important for cell division. Because activation of the Shh pathway is a feature of diverse human cancers, selective stimulation of proliferation by Shh-proteoglycan interactions may also figure prominently in neoplastic growth.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteoglicanas
/
Sistema Nervoso Central
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Regulação da Expressão Gênica no Desenvolvimento
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Proteínas Hedgehog
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Mitose
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article