Recombinant Human Wnt-7a Protein

Human Wnt-7a is one of about 19 vertebrate members of the Wingless-type MMTV integration site (Wnt) family of highly conserved cysteine-rich secreted glycoproteins important for normal developmental processes (1). Wnts bind to receptors of the Frizzled family in conjunction with low-density lipoprotein receptor-related proteins (LRPs). Downstream effects of Wnt signaling occur through activation of one of three different intracellular pathways: the canonical Wnt pathway, Wnt/Ca²⁺ pathway, and planar cell polarity. The highly transforming Wnts, including Wnt-1, -3, -3a, -7a and -8 activate the canonical pathway, which regulates beta ‑catenin-mediated gene expression (1, 2). Human Wnt-7a is a 48 kDa secreted glycoprotein containing 24 cysteine residues that is expressed by epithelial and epithelially-derived cells of the placenta, kidney, testis, uterus, fetal lung and fetal and adult brain (3, 4). Palmitate modification of a cysteine residue has been shown for Wnt-3a; this site is conserved on all Wnts and is Cys73 on Wnt7a (5). When modified, increased hydrophobicity and activity is expected. Human Wnt-7a shows 97% aa identity with mouse, rat and dog Wnt-7a and 92% aa identity with chicken Wnt-7a. During development, Wnt7a is expressed by the dorsal ectoderm and drives expression of homeodomain transcription factors that control effectors important in patterning and cell fates in adjacent mesenchyme (6 - 10). When Wnt-7a is deleted, mice show disruption of dorsalization and anterior/posterior patterning during limb development and abnormalities in the reproductive tract (6 - 10). Wnt-7a is frequently downregulated in leukemia and lung cancers, potentially affecting homeobox (HOX) gene expression, differentiation state and growth control (11, 12). Roles for Wnt-7a have also been shown during formation of neural synapses, response of the uterus to estrogen and inflammatory cartilage destruction (10, 13, 14).