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Cardiomyocyte Differentiation through BMP Receptors

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Description

BMP (Bone Morphogenetic Protein) Receptors are essential, beyond the egg cylinder stage, for myocyte-dependent functions and signals in cardiac organogenesis. ALK3 (Activin Receptor-Like Kinase-3) is specifically required at mid-gestation for normal development of the trabeculae, compact myocardium, interventricular septum and endocardial cushion. The invariable defects in myocardium results from congenital deletion of ALK3 and this provide strong support for its assessment as a candidate gene in human congenital heart disease. BMPs like BMP2, BMP4 and BMP5, BMP7, BMP10, bind to Serine/threonine kinase receptors, Type-I (ALK3 and ALK6) and Type-II, BMPR2 (Bone Morphogenetic Protein Receptor Type-II), respectively, and form a heteromeric signaling complex acting in series (Ref.1). In the presence of ligand, the Type-II receptor phosphorylates the Type-I receptors, which activate [...]

References:

1.Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3.
Gaussin V, Van de Putte T, Mishina Y, Hanks MC, Zwijsen A, Huylebroeck D, Behringer RR, Schneider MD.
Proc. Natl. Acad. Sci. U S A. 2002 Mar 5;99(5):2878-83.
2.Bone morphogenetic proteins induce cardiomyocyte differentiation through the mitogen-activated protein kinase kinase kinase TAK1 and cardiac transcription factors Csx/Nkx-2.5 and GATA-4.
Monzen K, Shiojima I, Hiroi Y, Kudoh S, Oka T, Takimoto E, Hayashi D, Hosoda T, Habara-Ohkubo A, Nakaoka T, Fujita T, Yazaki Y, Komuro I.
Mol. Cell Biol. 1999 Oct;19(10):7096-105.
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