Role of the novel protein family CAMSAP in heart, muscle and tracheal development

Ut Southwestern Medical Center, Dallas TX

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Identifying the mechanisms that govern heart development is a necessary step to advance our understanding of congenital heart diseases in humans. Since the molecular mechanisms regulating heart development are well conserved between insects and mammals, the powerful genetic tools in Drosophila can be used to identify novel regulators of cardiogenesis. We recently performed a genetic screen for regulators of embryonic heart development in Drosophila and identified over 120 genes whose function is required for proper cardiogenesis. One of these regulators, a novel gene named dCAMSAP, is expressed in discrete domains of the embryonic mesoderm including the heart and muscle precursor cells as well as in the embryonic tracheal system. Embryos bearing a loss-of-function mutation in dCAMSAP do not complete heart closure which causes the heart to tear as the mesoderm extends along the anterior-posterior axis of the embryo. Since the formation of a linear heart tube is a common developmental event in flies and vertebrates, the role of CAMSAP proteins may be highly conserved. In addition to heart closure defects, dCAMSAP mutants show developmental defects in muscles analogous to vertebrate skeletal muscle including both myoblast fusion defects and myotube guidance defects. Finally, the morphology of the insect respiratory system (the tracheal system), whose development is similar to vertebrate angiogenesis, is also affected in dCAMSAP mutant embryos. dCAMSAP is a member of a well conserved yet completely novel protein family with representative members in both humans and mice. The overall goal of this project is to define the molecular mechanisms whereby dCAMSAP regulates heart, skeletal (somatic) muscle, and tracheal system development and to assess the extent to which these mechanisms have been conserved in mammals. These studies will provide fundamental insights into the mechanisms regulating cardiovascular and skeletal muscle development and disease. [unreadable] [unreadable] [unreadable]