522 Leon Johnson Hall
Our lab studies the roles of cell-cell adhesion molecules in the formation of the vertebrate nervous system.
During embryonic development, cells destined to develop into discrete tissues must recognize and adhere to one another. These adhesive events are mediated by proteins found on the surfaces of cells, examples of which are the cadherins. Cadherins constitute a large family of transmembrane proteins that play essential roles in establishing adherens junctions between neighboring cells. Our lab studies the role of cadherins in embryonic development, with particular emphasis on the formation of the early vertebrate nervous system in frogs (Xenopus laevis) and chicken embryos.
We have isolated several novel cadherin family members, termed protocadherins, from both frog and chicken embryos. Our research currently centers on two of these protocadherins: NF-protocadherin (NFPC) isolated from frog embryos and chick protocadherin-1 (cPcdh1) isolated from chicken embryos, focusing on both their roles in the formation of the early nervous system and the mechanisms by which they achieve cell adhesion and cell signaling. For example, NFPC is expressed in the embryonic ectoderm in frogs and our studies have shown that it functions to mediate cell adhesion during formation of the neural tube and epidermis. Current research on NFPC focuses on the interactions between NFPC and a cytosolic co-factor TAF1/Set, as we seek to understand how changes in cell adhesion result in alterations in cellular differentiation. The second protocadherin we study, cPcdh1, is expressed in migrating neural crest cells in the chicken embryo. Current research centers on the role of cPcdh1 in neural crest migration and the establishment of the peripheral nervous system. By altering the expression of cPcdh1 in chicken embryos, using in ovo electroporation, we have shown that cPcdh1 plays an important role in mediating cell-cell adhesion as neural crest cells cease migrating and aggregate to form the dorsal root ganglia. Results from these studies will provide insights into the molecular mechanisms by which the vertebrate nervous system forms, as well as an understanding of how the adhesion between neighboring cells contributes to cellular differentiation and tissue histogenesis.
Bononi, J., A. Cole, P. Tewson, A. Schumacher and R. Bradley. 2008. Chicken protocadherin-1 functions to localize neural crest cells to the dorsal root ganglia during PNS formation. Mech. Devel. 125:1033-1047.
Piper, M., A. Dwivedy, L. Leung, R.S. Bradley and C.E. Holt. 2008. NF-protocadherin and TAF1 regulate retinal axon initiation and elongation in vivo. J. Neurosci. 28:100-105.
Kasemeier-Kulesa, J.C., R. Bradley, E.B. Pasquale, F. Lefcort, and P.M. Kulesa. 2006. Eph/ephrins and N-cadherin coordinate to control the pattern of sympathetic ganglia. Development. 133: 4839-47.
Rashid, D, K. Newell, L. Shama and R.S. Bradley. 2006. A requirement for NF-protocadherin and TAF1/Set in cell adhesion and neural tube formation. Developmental Biology, 291:170-181.
Heggem, M.A. and R.S. Bradley. 2003. The cytoplasmic domain of Xenopus NF-protocadherin interacts with TAF1/Set. Developmental Cell, 4(3): 419-429
Bradley, R.S., A. Espeseth, and C. Kintner. 1998. NF-protocadherin, a novel member of the cadherin superfamily, is required for Xenopus ectodermal differentiation. Current Biology, 8:325-334.
Riehl, R., K. Johnson, R. Bradley, G.B. Grunwald, E. Cornel, A. Lilienbaum, and C. Holt. 1996. Cadherin function is required for axon outgrowth in retinal ganglion cells in vivo. 1996. Neuron, 17: 837-848.
B.S. Biology, Carroll College, Helena, MT
Ph.D. Cell Biology and Genetics, Cornell University Medical College, New York, NY
Postdoctoral study in Developmental Biology, The Salk Institute, La Jolla, CA
Advanced Cell and Molecular Biology
Genes and Cancer