Cloning and Expression of the Wnt Antagonists Sfrp-2 and Frzb during Chick Development

Abstract

The Wnt genes are known to play fundamental roles during patterning and development of a number of embryonic structures. Receptors for Wnts are members of the Frizzled family of proteins containing a cysteine-rich domain (CRD) that binds the Wnt protein. Recently several secreted frizzled-related proteins (Sfrps) that also contain a CRD have been identified and some of these can both bind and antagonise Wnt proteins. In this paper we report the expression patterns of the chick homologues of Frzb, a known Wnt antagonist, and Sfrp-2. Both genes are expressed in areas where Wnts are known to play a role in development, including the neural tube, myotome, cartilage, and sites of epithelial-mesenchymal interactions. Initially, Sfrp-2 and Frzb are expressed in overlapping areas in the neural plate and neural tube, whereas later, they have distinct patterns. In particular Sfrp-2 is associated with myogenesis while Frzb is associated with chondrogenesis, suggesting that they play different roles during development. Finally, we have used the early Xenopus embryo as an in vivo assay to show that Sfrp-2, like Frzb, is a Wnt antagonist. These results suggest that Sfrp-2 and Frzb may function in the developing embryo by modulating Wnt signalling.

Diversity in the molecular and cellular strategies of epithelium-to-mesenchyme transitions: Insights from the neural crest

“…This is in particular the case of the Wnt antagonist Frzb-1, which is strongly expressed in the dorsal neural tube at the time of NC cell delamination. [114][115][116] Recent, interesting studies in the Xenopus embryo demonstrated that Frzb-1 promotes the dissolution of the basal lamina at the junction between the ectoderm and endoderm in the primary mouth primordium by decreasing levels of fibronectin and laminin transcripts. 117 Consistent with this view, overstimulation of the Wnt signaling pathway in vitro by LiCl or exogenous Wnt-1 or in vivo after electroporation of Wnt-1 or of a constitutively active form of β-catenin has been found to cause a marked inhibition of trunk NC cell delamination in birds.…”

Discovery of distinctive gene expression profiles in rheumatoid synovium using cDNA microarray technology: evidence for the existence of multiple pathways of tissue destruction and repair

“…31 Tightly controlled expression of agonists and antagonists of the wnt signaling pathway is crucial for tissue differentiation as is observed for DDK-1, a potent antagonist of wnt signaling controlling head formation in Xenopus. 32 The expression of the wnt antagonists DKK3 and SFRP-2 33 indicates that synovial cells are undergoing developmental changes in those tissues with little immune activation. It has been suggested before that synoviocytes may perpetuate disease by an autonomous growth and activation process in late stage RA.…”

The Secreted Frizzled Related Protein 2 (SFRP2) Gene Is a Target of the Pax2 Transcription Factor

“…Cell lines used for analysis included clone 46m Cells and Pax2 retrovirally transformed cells (designated clones 5,8,12,13,24,26,27,28). Each 100-mm plate contained 1 ϫ 10 7 cells.…”

“…One of the most prominent genes activated in response to Pax2 encodes the secreted frizzled related protein, Sfrp2. The Sfrp proteins can negatively regulate signaling through sequestration of the Wnt ligands in the extra cellular space (7,28,29). Sfrp2 is expressed in the early polarized epithelial vesicle, in a subset of Pax2-expressing epithelia.…”