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6 41513 classical studies leading to idenjcajon of

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Unformatted text preview: cifies Cardiogenic Mesoderm Anterior Mes/endoderm Epiblast/ ESCs/iPSCs Later streak Anterior HIGH Endoderm Head Mesoderm Cardiac Nodal/TGFβ Early streak Mesoderm Posterior Ectoderm Anterior Body Mesoderm Posterior LOW Posterior BMP and Wnt Have a Posteriorizing Influence, and Oppose the Anteriorizing Effect of Nodal/TGFβ Mes/endoderm Epiblast/ ESCs/iPSCs Anterior HIGH LOW Endoderm Head Anterior Mesoderm Cardiac Nodal/TGFβ Anterior Later streak Mesoderm Posterior Ectoderm Body Mesoderm BMP/Wnt Early streak Posterior LOW HIGH Posterior Signals that Direct Cardiogenic Mesoderm to Become Cardiac Cardiogenic mesoderm Nodal/TGFβ signalling ?? 6 4/15/13 Classical Studies Leading to IdenJficaJon of Heart ­Inducing Signals •  •  •  •  William M. Copenhaver (1926) exJrpated the heart forming region in axolotls, and observed hearts formed (albeit infrequently) from Jssue he thought was originally more posterior Gunnar Ekman (1920s) cultured heart rudiments alone and found they could beat. He noJced a posiJve influence of endoderm, but did not consider it inducJve. In 1927, showed that mesoderm located more laterally could be induced to form heart if transplanted into the heart forming region. Robert L. Bacon (1945) transplanted non ­ cardiac mesoderm to the heart region in axolotls, and found it could be induced to form heart Anton Jacobson (1968) showed that removal of endoderm in newts prevented heart formaJon during a criJcal window, matching approximately the Jming when the heart field would acquire “self ­differenJaJon” capability (image on right). Discovery of Heart ­Inducing Molecules •  Wnt Inhibitors. Marvin et al. and Schneider and Mercola showed that natural Wnt inhibitors, including Dickkopf ­1 induced heart Jssue from non ­cardiac mesoderm in chick and frog embryos •  Nodal/TGFβ inhibitors. Foley and Mercola discovered that Cerberus ­1, a natural inhibitor of Nodal is a strong inducer at a slightly earlier Jme •  The Wnt and Nodal/TGFβ inhibitors are endodermally ­derived heart inducing signals Embryological Studies Have IdenJfied Many Genes and Proteins Involved in Heart FormaJon ventral dorsal Inject syntheJc mRNA encoding signaling proteins into non ­cardiac, non ­pancreas regions of Xenopus embryos heart ­forming region pancreas, liver, lung forming region Isolate and culture non ­cardiac Jssue Examine Jssue for evidence of heart ­specific differenJa...
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