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1.
Development ; 145(14)2018 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-30061166

RESUMO

The Myc transcriptional regulators are implicated in a range of cellular functions, including proliferation, cell cycle progression, metabolism and pluripotency maintenance. Here, we investigated the expression, regulation and function of the Myc family during mouse embryonic axis elongation and segmentation. Expression of both cMyc (Myc - Mouse Genome Informatics) and MycN in the domains in which neuromesodermal progenitors (NMPs) and underlying caudal pre-somitic mesoderm (cPSM) cells reside is coincident with WNT and FGF signals, factors known to maintain progenitors in an undifferentiated state. Pharmacological inhibition of Myc activity downregulates expression of WNT/FGF components. In turn, we find that cMyc expression is WNT, FGF and Notch protein regulated, placing it centrally in the signalling circuit that operates in the tail end that both sustains progenitors and drives maturation of the PSM into somites. Interfering with Myc function in the PSM, where it displays oscillatory expression, delays the timing of segmentation clock oscillations and thus of somite formation. In summary, we identify Myc as a component that links NMP maintenance and PSM maturation during the body axis elongation stages of mouse embryogenesis.


Assuntos
Relógios Biológicos/genética , Padronização Corporal/genética , Proteínas CLOCK/genética , Mesoderma/citologia , Mesoderma/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais/genética , Células-Tronco/metabolismo , Animais , Proteínas CLOCK/metabolismo , Diferenciação Celular , Regulação para Baixo/genética , Embrião de Mamíferos/metabolismo , Feminino , Fator 8 de Crescimento de Fibroblasto/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Mesoderma/embriologia , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Somitos/embriologia , Somitos/metabolismo , Células-Tronco/citologia , Cauda/embriologia , Proteínas Wnt/metabolismo
2.
Development ; 142(13): 2291-303, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25995356

RESUMO

Notochord-derived Sonic Hedgehog (Shh) is essential for dorsoventral patterning of the overlying neural tube. Increasing concentration and duration of Shh signal induces progenitors to acquire progressively more ventral fates. We show that Notch signalling augments the response of neuroepithelial cells to Shh, leading to the induction of higher expression levels of the Shh target gene Ptch1 and subsequently induction of more ventral cell fates. Furthermore, we demonstrate that activated Notch1 leads to pronounced accumulation of Smoothened (Smo) within primary cilia and elevated levels of full-length Gli3. Finally, we show that Notch activity promotes longer primary cilia both in vitro and in vivo. Strikingly, these Notch-regulated effects are Shh independent. These data identify Notch signalling as a novel modulator of Shh signalling that acts mechanistically via regulation of ciliary localisation of key components of its transduction machinery.


Assuntos
Proteínas Aviárias/metabolismo , Cílios/metabolismo , Proteínas Hedgehog/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Biomarcadores/metabolismo , Linhagem da Célula , Embrião de Galinha , Fibroblastos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Fatores de Transcrição Kruppel-Like/metabolismo , Camundongos , Neurônios Motores/metabolismo , Células NIH 3T3 , Proteínas do Tecido Nervoso/metabolismo , Placa Neural/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Tubo Neural/metabolismo , Notocorda/metabolismo , Receptores Notch/antagonistas & inibidores , Receptor Smoothened , Proteína Gli3 com Dedos de Zinco
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