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First published online 27 August 2003
doi: 10.1242/dev.00686

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Carboxypeptidase Z (CPZ) modulates Wnt signaling and regulates the development of skeletal elements in the chicken

¹ Max Planck Institute of Experimental Endocrinology, Hannover, Germany 30625
² Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030, USA
³ Institute of Molecular Biology, Medical School Hannover, Hannover, Germany 30625

^* Author for correspondence (e-mail: gregor.eichele{at}mpihan.mpg.de)

Accepted 25 June 2003

Carboxypeptidase Z (CPZ) is a secreted Zn-dependent enzyme whose biological function is largely unknown. CPZ has a bipartite structure consisting of an N-terminal cysteine-rich domain (CRD) and a C-terminal catalytic domain. In the early chicken embryo CPZ is initially expressed throughout the somites and subsequently becomes restricted to the sclerotome. To initiate a functional analysis of CPZ, a CPZ producing retroviral vector was applied to the presomitic mesoderm at the level of the future wing. This resulted in a loss of the scapular blade and of rostral ribs. Such dysmorphogenesis is preceded by ectopic Pax3 expression in the hypaxial part of the dermomyotome, a region from which the blade of the scapula normally derives. A mutant CPZ, lacking a critical active site glutamate, fails to induce Pax3 expression and does not cause skeletal defects. The induction of Pax3, a Wnt-responsive gene in somites, and the presence of a CRD prompted us to examine whether CPZ affects Wnt signaling. In an in vitro assay we found that CPZ, but not its inactive mutant form, enhances the Wnt-dependent induction of the homeobox gene Cdx1. In addition, immunoprecipitation experiments suggest that the CRD of CPZ acts as a binding domain for Wnt. Taken together these data provide the first evidence for CPZ playing a role in Wnt signaling.

Key words: Carboxypeptidase Z, Somite, Sclerotome, Pax3, Pax1, Scapula, Rib, Wnt, Cysteine-rich-domain, CRD, AER, Paraxial head mesoderm, Chicken

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