Abstract:In the chick, heart mesoderm is induced by signals from the anterior endoderm. Although BMP-2 is expressed in the anterior endoderm, BMP activity is necessary but not sufficient for heart formation. Previous work from our lab has suggested that one or more additional factors from anterior endoderm are required. Crescent is a Frizzled-related protein that inhibits Wnt-8c and is expressed in anterior endoderm during gastrulation. At the same stages, expression of Wnt-3a and Wnt-8c is restricted to the primitive … Show more
“…Dkk1 and crescent (a Wnt inhibitor of the sFRP family) are able to induce myocardial tissue formation from putative noncardiogenic mesodermal tissue (Marvin et al, 2001;Schneider and Mercola, 2001). While this supports the idea that Wnt inhibition is required for formation of yet another organ of anterior origin, Dkk1 may not be essential for this process, or act redundantly with other Wnt inhibitors, since Dkk1 mutant mice have apparently normal hearts.…”
“…Dkk1 and crescent (a Wnt inhibitor of the sFRP family) are able to induce myocardial tissue formation from putative noncardiogenic mesodermal tissue (Marvin et al, 2001;Schneider and Mercola, 2001). While this supports the idea that Wnt inhibition is required for formation of yet another organ of anterior origin, Dkk1 may not be essential for this process, or act redundantly with other Wnt inhibitors, since Dkk1 mutant mice have apparently normal hearts.…”
“…The antagonist Dkk1 interacts with LRP5/6, which in turn acts as high affinity antagonists to the frizzled receptors (Bafico et al, 2001;Mao et al, 2001). Based upon previous studies, canonical Wnt signaling is important for cardiac cell differentiation (Linask, 1992a;Linask et al, 1997;Marvin et al, 2001;Schneider and Mercola, 2001;Tzahor and Lassar, 2001). The lithium/Wnt-3A experiments reported here show that it is an early canonical Wnt-mediated anteroposterior (AP) signaling wave that is necessary and coordinated with the other specified factors to define cardiac cell fate and the boundaries of the cardiac compartment within the mesoderm.…”
Section: Ap Progression Of Lithium Repression Of Cardiomyogenesismentioning
Members of both Wnt and bone morphogenetic protein (BMP) families of signaling molecules are important in heart development. We previously demonstrated that -catenin, a key downstream intermediary of the canonical Wnt signaling pathway, delineates the dorsal boundary of the cardiac compartments in an anteroposterior progression. We hypothesized the progression involves canonical Wnt signaling and reflects development of the primary body axis of the embryo. A similar anteroposterior signaling wave leading to cardiac cell specification involves inductive signaling by BMP-2 synthesized by the underlying endoderm in anterior bilateral regions. Any molecule that disrupts the normal balance of Wnt and BMP concentrations within the heart field may be expected to affect early heart development. The canonical Wnt signaling step mimicked by lithium involves inactivation of glycogen synthase kinase-3 (GSK-3; Klein and Melton [1996] Proc. Natl. Acad. Sci. U. S. A. 93:8455-8459). We show that lithium, Wnt-3A, and an inhibitor of GSK-3, SB415286, affect early heart development at the cardiac specification stages. We demonstrate that normal expression patterns of key signaling molecules as Notch-1 and Dkk-1 are altered in the anterior mesoderm within the heart fields by a one-time exposure to lithium, or by noggin inhibition of BMP, at Hamburger and Hamilton (HH) stage 3 during chick embryonic development. The severity of developmental defects is greatest with exposure to lithium or Wnt-3A at HH stage 3 and decreases at HH stage 4. Taken together, our results demonstrate that there are temporal-specific responses and differential sensitivities to lithium/Wnt-3A exposure during early heart development.
“…Thus, screening with these in vitro-induced hearts has contributed new knowledge as to when and how the components of the hyaluronan matrix function in cardiogenesis. These systems also permit more detailed analyses of the roles of Wnt signaling (Marvin et al, 2001;Schneider and Mercola, 2001;Tzahor and Lassar, 2001) and transcription factors, such as Nkx2.5 (Durocher et al, 1997;Reecy et al, 1999) and GATA4 (Grepin et al, 1995(Grepin et al, , 1997Jiang et al, 1999) in cardiogenesis. In the recent study, we examined a comprehensive set of cardiogenesis-related genes using an in vitro Xenopus-based system and microarrays.…”
Section: Cardiac Organ Engineering: An In Vitro-generated Frog Heartmentioning
Amphibians have been used for over a century as experimental animals. In the field of developmental biology in particular, much knowledge has been accumulated from studies on amphibians, mainly because they are easy to observe and handle. Xenopus laevis is one of the most intensely investigated amphibians in developmental biology at the molecular level. Thus, Xenopus is highly suitable for studies on the mechanisms of organ differentiation from not only a single fertilized egg, as in normal development, but also from undifferentiated cells, as in the case of in vitro organogenesis. Based on the established in vitro organogenesis methods, we have identified many genes that are indispensable for normal development in various organs. These experimental systems are useful for investigations of embryonic development and for advancing regenerative medicine. Developmental Dynamics 238:1309 -1320, 2009.
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