Mesodermal patterning modules in the evolution and development of the tetrapod pectoral region

Wesleyan University, Middletown CT

Investigators

Abstract

Three primary tissues present in early embryos, endoderm, ectoderm and mesoderm, ultimately develop into all body parts of vertebrates. Shortly after initial mesoderm is established, two distinct populations of mesoderm separate, providing the cells for axial and appendicular mesodermal tissues. Extensive integration occurs between cells within these two forms of mesoderm to ensure that the musculoskeletal system forms correctly. Despite recent advances in knowledge of the genetics of muscle and bone formation in the limbs and the vertebral axis, how integration of the axial and appendicular mesodermal tissues is regulated is still largely unknown. The research proposed here focuses on the changes that occur at the mesodermal boundary between axial and appendicular systems where musculoskeletal integration is achieved. The proposal focuses on the pectoral region where formation of the forelimb is functionally linked to the axial system. The interface between somitic and lateral plate mesoderm is called the lateral somitic frontier. It is proposed that genetic patterning information is regulated independently in distinct mesodermal domains, distinguishing the two domains as evolutionarily conserved modules in developmental. Transgenic mice will be used to eliminate specific patterning genes in these distinct mesodermal domains independently. Transplant surgeries in amphibian embryos will map the frontier in amphibians to determine the evolutionary basal state for the tetrapod lineage. This research will have broad impact on the developmental biology community by providing detailed embryonic context in which to study the function of molecular factors involved in patterning the mesoderm. The data generated will be used in collaboration to build, test, and increase the power of new biological ontologies now under construction (e.g. AmphibAnat) and be available to the greater community. This work will also provide broad based training experiences for undergraduate and graduate students including hands on experience in embryology, molecular biology, and computer assisted 3D modeling.