Assistant Professor

B.A. State University of New York, Oswego, 1993
Ph.D. University of Wisconsin, Madison, 1999

Research Interests:

Limb development
Organogenesis
Mouse genetics
Integration of signaling pathways

Current Research:

We use mice to study organogenesis during development, with a particular emphasis on limb formation, patterning and growth. Limbs have played a crucial role in animal evolution as the adaptive evolution of vertebrates to aquatic, terrestrial, and aerial environments involved the acquisition and modification of their limbs. Despite current knowledge of the genes controlling patterning along the primary axes in the developing limb, there are gaps in our understanding of how a limb is built. For example, it is not known how earlyin anterior-posterior or dorsal-ventral identity is imparted to the limb. There is much to learn about the early stages of limb development and the identification of new genes required for limb growth and patterning is needed.

To broaden our insight into the genetic mechanisms underlying limb formation and patterning I performed a forward genetics screen in the laboratories of Kathryn Anderson and Lee Niswander in the mouse. Previous studies have shown that forward genetics screens are feasible in the mouse and are an excellent, unbiased method to uncover factors critical for a wide variety of developmental processes. In a screen of ~100 pedigrees I identified three recessive mouse mutants with defects in various aspects of limb development. Two of these, hitchhiker and kerouac show preaxial polydactyly and affect anterior-posterior patterning. In contrast, shorthand was identified by defects in proximal-distal outgrowth of the limb. The genomic regions linked to these mutants do not contain known limb patterning genes indicating that we have identified novel genes required for limb development. The characterization and cloning of the genes affected in these mutants should provide a better understanding of anterior-posterior and proximal-distal patterning during limb development.

The lab is also continuing to work on a pair of mutants that were identified in two independent screens. These mutants affect the low density lipoprotein related 4 gene (Lrp4). Lrp4 is essential for proper patterning along all three of the major axes during limb development. In addition, Lrp4 is required for neuromuscular junction formation and normal development of ectodermal organs such as mammary buds, teeth and vibrissae. We are interested in defining how Lrp4 regulates the development of these vastly different organs and in determining which signaling pathways Lrp4 interacts with.