Human Molecular Genetics, Vol 7, 1161-1167, Copyright © 1998 by Oxford University Press
R Yavari, C Adida, P Bray-Ward, M Brines and T Xu
The development of the sympathetic nervous system involves cell-cell
interactions that regulate the fate and migration of progenitor neural
cells. Recent evidence shows that focal membrane-bound protease activity is
critical for such interactions. The Drosophila kuzbanian (kuz) gene is
required in neurogenesis and encodes a highly conserved, membrane-bound
metalloprotease- disintegrin closley related to theTNF-
alphaconvertingenzyme (TACE). We have characterized the human and mouse kuz
homologs and mapped human kuz to chromosome 15q22. During mouse embryonic
development Kuz is expressed mainly in the sympathoadrenal and olfactory
neural precursors. Once sympathoadrenal cells differentiate into chromaffin
cells in the adult adrenal medulla, they no longer express Kuz. However, we
found that tumors of sympathoadrenal origin, such as pheochromocytomas and
neuroblastomas, overexpress Kuz. Further, transfection of a kuz construct
lacking the protease domain, but not the full-length construct, induces
neurite formation in PC12 chromaffin tumor cells. Taken together our
results suggest a critical role for Kuz in regulation of sympathoadrenal
cell fate.
ARTICLES
Human metalloprotease-disintegrin Kuzbanian regulates sympathoadrenal cell fate in development and neoplasia
Howard Hughes Medical Institute and Department of Genetics, Yale School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536-0812, USA.
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