組織工学・再生医療 【おまけ】
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Application of BMP-2–soaked beads in vivo has also been used to induce the ectopic expression of cardiac transcription factors, and the administration of soluble BMP-2 or BMP-4 to explant cultures induces full cardiac differentiation in stage 5 to 7 anterior medial mesoderm, a tissue that is normally not cardiogenic. (Circ Res 2006;98:1002)
Application of BMP-2-soaked beads in vivo elicits ectopic expression of the cardiac transcription factors CNkx-2.5 and GATA-4. Furthermore, administration of soluble BMP-2 or BMP-4 to explant cultures induces full cardiac differentiation in stage 5 to 7 anterior medial mesoderm, a tissue that is normally not cardiogenic. (Genes Dev 1997;11: 451)
In Xenopus gastrula-stage embryos, Noggin and other BMP inhibitors are secreted by the Spemann organizer and induce neural tissue from dorsal ectoderm by inhibiting ectodermal BMPs.(Circ Res 2006;98:1002)
In Xenopus gastrula stage embryos, Noggin is secreted by the Spemann organizer and induces neural tissue from dorsal ectoderm by inhibiting ectodermal BMPs. (Neuron 2000;28:713)
The Wnt/beta-catenin pathway (canonical Wnt pathway) regulates cell adhesion, morphology, proliferation, migration, and structural remodeling. The major components of this network are the Wnt ligands, which bind to frizzled receptors at the cell surface.··· ···Activation of Wnt signaling down regulates the intracellular degradation of beta-catenin, allowing translocation to the nucleus and transcription factor activation in conjunction with cotranscription factors Lefs and Tcfs. (Circ Res 2006;98:1002)
The Wnt–beta-catenin pathway regulates cell adhesion, morphology, proliferation, migration and structural remodeling. The aspects of the canonical and non-canonical pathways are reviewed here. The major components of this network are the Wnt ligands which bind to frizzled receptors at the cell surface. Activation of Wnt signaling down regulates the intracellular beta-catenin degradation component, allowing beta-catenin levels to accumulate within the cell. At normal levels, beta-catenin associates at the intracellular side of the membrane with cadherins to promote cell adhesion and with the actin microfilament cytoskeletal network to control cell shape. If beta-catenin levels become elevated, it can begin to accumulate within the cell nucleus and activate transcription in conjunction with co-transcription factors Lefs/Tcfs. (Growth Factors 2005;23:111)
Marvin et al reported ······ that ectopic Wnt signals can repress heart formation from anterior mesoderm in vitro and in vivo. In addition, the forced expression of either Wnt3A or Wnt8 promoted the development of primitive erythrocytes from the precardiac region. ··· ···These findings indicated thatinhibition of Wnt signaling by diffusion of Dkk-1 and Crescent from the organizer promotes heart formation in the anterior lateral mesoderm, whereas active Wnt signaling in the posterior lateral mesoderm promotes blood development. (Circ Res 2006;98:1002)
Furthermore, we have found that ectopic Wnt signals can repress heart formation from anterior mesoderm in vitro and in vivo and that forced expression of either Wnt-3a or Wnt-8c can promote development of primitive erythrocytes from the precardiac region. We conclude that inhibition of Wnt signaling promotes heart formation in the anterior lateral mesoderm, whereas active Wnt signaling in the posterior lateral mesoderm promotes blood development.(Genes Dev 2001;15:316)
Subsequent loss- and gain-of-function experiments showed that Wnt11 is required for heart formation in Xenopus embryos and is sufficient to induce a contractile phenotype in embryonic explants via noncanonical Wnt signaling, which is independent of beta-catenin but involves protein kinase C and JNK.Moreover, they reported that treating the mouse embryonic carcinoma stem cell line P19 with murine Wnt11-conditioned medium triggers cardiogenesis,suggesting that the function of Wnt11 in heart development is conserved in higher vertebrates. ….. Together, these results indicated that cardiac development requires noncanonical Wnt signal transduction. (Circ Res 2006;98:1002)
Here we show, through loss- and gain-of-function experiments, that XWnt-11 is required for heart formation in Xenopus embryos and is sufficient to induce a contractile phenotype in embryonic explants. Treating the mouse embryonic carcinoma stem cell line P19 with murine Wnt-11 conditioned medium triggers cardiogenesis, which indicates that the function of Wnt-11 in heart development has been conserved in higher vertebrates. XWnt-11 mediates this effect by non-canonical Wnt signalling, which is independent of beta-catenin and involves protein kinase C and Jun amino-terminal kinase. Our resultsindicate that the cardiac developmental program requires non-canonical Wnt signal transduction. (Nature 2002;418:636)
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