Most organisms with arms or legs hatch, or are born, with limbs that are largely functional. Accordingly, these animals make their limbs during embryonic development. The study of how limbs develop has taught us much about how cells interact and how changes in developmental processes result in different limb shapes. For example, differences between the leg of a mouse and the wing of a bat can be traced to subtle changes in limb development. Surprisingly missing from our understanding is how animals, such the tadpoles of frogs, are capable of making a limb when they are no longer embryos. This project aims to discover what part of the tadpole body generates the limbs of the frog prior to its metamorphosis. Combining traditional methods with newly available genetic tools this research will reveal what cells in the tadpole generate the limb and how the genes that regulate its development are controlled. The findings from this work will reveal alternative methods by which nature makes the limbs of animals. Further, they will show us the possibilities of growing limbs during different stages of an animal’s life according to the rules of nature. Finally, this work will have impacts beyond scientific discoveries as many of the experiments will be carried out by undergraduates from a woman centered university, student researchers that comprise the next generation of scientists.
Studies of the vertebrate limb have provided a deep understanding of the cellular, genetic, and molecular mechanisms that generate an appendage. They have also revealed how the basic pattern of tetrapod limbs can been modified through evolution to give rise to the myriad of arms, legs, wings, and fins we observe in nature. The majority of limb experimentation has been in animals where the limb forms early in embryogenesis. Yet, several tetrapods, most notably frogs, form their limbs well after embryonic patterning and differentiation has occurred. Surprisingly, we know very little about the processes that initially direct limb formation in amphibian tadpoles since most limb research in these animals has focused on regeneration. Recent technological advancements now allow for us to use the frog Xenopus to determine how a tadpole generates a limb when embryonic tissue is no longer present. Overall, this project seeks to answer this question by testing the hypotheses that frogs generate their limbs from multiple embryonic origins and genetically delay the typical tetrapod limb initiation program. This hypothesis will be tested by first determining the embryological origins and induction stage of the limb buds. Then limb gene enhancers will be interrogated to discover how the initiation of frog limbs is controlled. Taken together, this work will provide a fuller understanding of tetrapod limb diversity and plasticity. Finally, the experiments conducted here will be at the forefront of developing new technologies for use by both the Xenopus community as well as those studying the limb more broadly.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
