My laboratory has studied molecular substrates of mammalian development. We identified a family of glycovariants of the extracellular matrix (ECM) proteoglycan, aggrecan, whose expression is regulated by neuronal activity early in an animal's life. Expression of the aggrecan glycoforms is regulated in parallel with critical period events and may play a role in stabilizing mature synaptic relationships. A related ECM protein, BEHAB/brevican, is expressed when glial cells travel during development and after brain injury. BEHAB/brevican is also expressed at very high levels in brain tumors, and can mediate the motility of tumor cells. A key feature of our work has been to bring biochemical and molecular biological techniques to the classical anatomical analysis of mammalian CNS development.
Matthews, R.T., G. Kelly, C. Zerillo, G. Gray, M. Tiemeyer and S. Hockfield. Aggrecan glycoforms contribute to the molecular heterogeneity of perineuronal nets. J. Neuroscience 22: 7536-7547 (2002).
Quinn, C.Q., E. Chen, T.G. Kinjo, G. Kelly, A.W. Bell, P.S. McPherson and S. Hockfield. TUC-4b, a novel TUC family variant, regulates neurite outgrowth and associates with vesicle in the growth cone. J. Neuroscience 23:2815-2823 (2003).
Viapiano, M.S., R.T. Matthews and S. Hockfield. A novel membrane-associated glycovariant of BEHAB/brevican is upregulated during rat brain development and in a rat model of invasive glioma. J. Biol.Chem. 278: 33239-33247 (2003).
Viapiano, M.S., W. Bi, J. Piepmeier, S. Hockfield and R.T. Matthews. Novel tumor-specific isoforms of BEHAB/brevican identified in human malignant gliomas. Cancer Research 65:6726-6733 (2005).
Dino, M. R., S. Harroch, S. Hockfield and R. T. Matthews. Monoclonal antibody Cat-315 detects a glycoform of receptor protein tyrosine phosphatase beta/phosphacan early in CNS development that localizes to extrasynaptic sites prior to synapse formation. Neuroscience 142: 1055-69 (2006).