Karen Symes
Associate Professor of Biochemistry
Department of Biochemistry
Boston University School of Medicine
Silvio Conte Building, K408
72 E. Concord Street
Boston, MA 02118
Phone: 617-638-4077
Fax: 617-638-5339
Email: symes@bu.edu
Education
BSc., University of Sussex, Brighton, UK
Ph.D. National Institute for Medical Research, Mill Hill, London, UK
Research Interest
The major goals of my laboratory are to understand the molecular basis of cell movements during embryonic development, and to identify the role of apoptosis in organogenesis focusing on the developing notochord, which ultimately forms part of the intervertebral discs of the spine.
1. We have shown that when signaling through the platelet-derived growth factor (PDGF) receptor is blocked in embryos of the frog, Xenopus laevis, mesoderm cell movements are inhibited. We are now using several strategies to dissect PDGF signaling in mesoderm cell movement.
When PDGF binds to its receptor, the receptor undergoes dimerization and the intrinsic tyrosine kinase activity in its cytoplasmic portion is activated. This results in autophosphorylation of specific tyrosine residues in the intracellular domain of the receptor. These phosphotyrosines serve as high affinity binding sites for signaling molecules including phosphatidylinositol-3 kinase (PI3K), RasGAP, SHP2, c-Src and phospholipase C gamma (PLC gamma). We are examining the role of each of these signaling molecules in Xenopus mesoderm cell movement. This project involves the activation of mutant PDGF receptors that can only bind specific signaling molecules in mesoderm cells in vitro and in vivo. The cells are being monitored by time-lapse micrography to detect changes in their shape and motility. Candidate downstream signaling effectors such as the Rho family of small GTP-binding proteins that are known modulators of the actin cytoskeleton are also being examined, as well as new factors that act to spatially and temporally localize PDGF signaling.
2. The mechanisms by which the spatial and temporal coordination of different developing tissues occur are largely unknown. Our recent evidence in Xenopus embryos suggests that apoptosis plays an essential role in at least one of these processes during the extension of the anterior posterior axis. We find that during normal development, notochord cells die by apoptosis. This apoptosis occurs in an anterior to posterior pattern that corresponds to a rapid increase in the extension of the notochord through vacuolization. Inhibition of this cell death in vivo causes the severe malformation of the notochord, a shortening of the anterior posterior axis, and adjacent tissues such as the somites are disorganized. The molecular mechanims that initiate, execute and control this apoptosis as well as the consequences of its disruption are being examined.
Representative Publications
Tahinci, E. and Symes, K. (2003) Distinct functions of Rho and Rac are required for convergent extension during Xenopus gastrulation. Dev. Biol. 259, 318-335
Nagel, T., Tahinci, E., Symes, K. and Winklbauer, R. (2004). Platelet derived growth factor signaling controls the directed migration of head mesoderm cells in Xenopus laevis embryos. Development 131, 2727-2736.
Van Stry, M., McLaughlin, K.A., Ataliotis, P. and Symes, K. (2004). The mitochondrial-apoptotic pathway is triggered in Xenopus mesoderm cells deprived of PDGF receptor signaling during gastrulation. Dev. Biol. 268, 232-242.
Van Stry, M., Kazlauskas, A., Schreiber, S.L., and Symes, K. (2005). Distinct Effectors Of PDGFR? Signaling Are Required For Cell Survival During Embryogenesis. Proc. Natl. Acad. Sci, 102, 8233-8238.
Ren, R., Nagel, M. Tahinci, E. Winklbauer, R. and Symes, K. (2006). Migrating anterior mesoderm cells and intercalating axial mesoderm cells have distinct responses to Rho and Rac during Xenopus gastrulation. Dev. Dyn. 235, 1090-1099.
Malikova, M.A., Van Stry, M. and Symes, K. (2007). Apoptosis regulates notochord development in Xenopus. Dev. Biol. 311, 434–448.
