DAN is a secreted glycoprotein related to Xenopus cerberus

Abstract

We report that DAN, a potential cell cycle regulator and tumour suppressor, is a secreted glycoprotein related to Xenopus cerberus. DAN, cerberus, its mouse relative Cer-1/cer-l/Cerberus-like/Cerr1, and the recently described factor DRM/Gremlin, appear to be members of the cystine knot superfamily, which includes TGF βs and BMPs. Like cerberus and mCer-1, DAN induced cement glands as well as markers of anterior neural tissue and endoderm in Xenopus animal cap assays, features of BMP signalling blockade. During mouse embryogenesis, Dan was expressed from E8.5 in cranial mesenchyme and somites, then later in limb and facial mesenchyme. The pattern in somites was highly dynamic, with transcripts initially localized to the caudal half of the nascent epithelial somite, then, after maturation, to sclerotomal cells adjacent to the neural tube. Dan was also expressed in the developing myotome. The expression domains include sites in which BMP inhibition is known to be important for development. Thus, DAN appears to be a secreted factor belonging to the cystine knot superfamily, and one of a growing number of antagonists acting to modulate BMP signalling during development.