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RUI: Elucidating The Role of Hoxa-5 In Cervical Somite Morphogenesis and Evolution

$407,198FY2008BIONSF

Barnard College, New York NY

Investigators

Abstract

One of the earliest events in animal development is the establishment of the main, head-to-tail body axis. Embryonic cells and tissues must receive a molecular "address" along this axis, and then develop appropriately for their location. In most animals, these processes are regulated at several steps by the highly conserved Hox gene family. Hox proteins regulate the expression of other, mostly unknown, genes, and play central roles in both the development and evolution of animal body plans. Despite enormous progress toward understanding the roles of Hox proteins in development and evolution, we still know relatively little about which cellular processes they regulate in the various tissues in which they act, especially in vertebrates. This project will examine the cellular processes regulated by one Hox gene, Hoxa5, during the development of vertebrate axial tissues (bone, muscle, and connective tissues of the vertebral column and ribs). Molecular genetic methods will be employed to ask (1) which cells within developing mouse express, or have a history of expressing, Hoxa5, (2) whether there a lineage relationship between cells that express Hoxa5 at different stages of embryogenesis, (3) how cells with a history of having expressed Hoxa5 differ from cells that do not, both in terms of their development and eventual fates, and finally, (3) how changes in Hoxa5 expression influence the differentiation of vertebral segments in chick embryos. Together, these approaches are aimed at teasing apart the elusive and context-dependent roles for this Hox protein in one embryonic tissue in which it acts. In addition, the genetic reagents produced by this work will be useful for future studies examining Hoxa5's roles in other tissues. This research will be conducted at Barnard College: an undergraduate, liberal arts college for women. Undergraduates will collaborate with the PI and a research technician in all aspects of this work, from experimental design to conducting experiments to analysis of results. The broader impacts of this study are (1) to provide new insight into how Hox proteins regulate patterning and differentiation of vertebrate tissues and (2) to provide a hands-on training experience for undergraduate researchers in a lab environment where they are the driving force behind the research.

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