Journal Article

Human Metalloprotease-Disintegrin Kuzbanian Regulates Sympathoadrenal Cell Fate in Development and Neoplasia

Reza Yavari, Colette Adida, Patricia Bray-Ward, Michael Brines and Tian Xu

in Human Molecular Genetics

Volume 7, issue 7, pages 1161-1167
Published in print July 1998 | ISSN: 0964-6906
Published online July 1998 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/7.7.1161
Human Metalloprotease-Disintegrin Kuzbanian Regulates Sympathoadrenal Cell Fate in Development and Neoplasia

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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 the TNF-α converting enzyme (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 neuro-blastomas, 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.

Journal Article.  0 words. 

Subjects: Genetics and Genomics

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