A mouse cerberus/Dan-related gene family

Dev Biol. 1999 May 1;209(1):98-110. doi: 10.1006/dbio.1999.9240.

Abstract

The Xenopus cerberus gene is able to induce ectopic heads in Xenopus embryos. At the time of its identification, cerberus shared significant homology with only one other protein, the putative rat tumor suppressor protein Dan. Sequence analysis has revealed that cerberus and Dan are members of a family of predicted secreted proteins, here called the can family. The identification of a can-family member in the nematode Caenorhabditis elegans, CeCan1, suggests that this family is of ancient origin. In the mouse, there are at least five family members: Cer1, Drm, PRDC, Dan, and Dte. These genes are expressed in patterns that suggest that they may play important roles in patterning the developing embryo. Cer1 marks the anterior visceral endoderm at E6.5. Dte is expressed asymmetrically in the developing node. Dan is first seen in the head mesoderm of early head fold stage embryos and Drm is expressed in the lateral paraxial mesoderm at E8.5. The region of homology shared by these genes, here called the can domain, closely resembles the cysteine knot motif found in a number of signaling molecules, such as members of the TGFbeta superfamily. Epitope-tagged versions of Cer1 show that, unlike in TGFbeta superfamily members, the cysteine knot motif is not processed away from a proprotein. Recent experiments in Xenopus have suggested that cerberus may act as an inhibitor of BMP signaling. To examine this further, the ability of Dan, Cer1, and human DRM to attenuate Bmp4 signaling has been assessed in P19 cells using pTlx-Lux, a BMP-responsive reporter. All three genes are able to inhibit Bmp4 signaling. These data suggest that the different family members may act to modulate the action of TGFbeta family members during development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arabidopsis Proteins*
  • Body Patterning*
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / metabolism
  • Cytokines
  • Immunoblotting
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Models, Genetic
  • Molecular Sequence Data
  • Multigene Family
  • Neoplastic Stem Cells
  • Plant Proteins / metabolism
  • Proteins / genetics*
  • Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Time Factors
  • Transforming Growth Factor beta*
  • Xenopus Proteins*

Substances

  • Arabidopsis Proteins
  • BMP2 protein, human
  • BMP4 protein, human
  • Bmp2 protein, mouse
  • Bmp2 protein, rat
  • Bmp4 protein, mouse
  • Bmp4 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • CER protein, Arabidopsis
  • Cytokines
  • Dte protein, mouse
  • Grem1 protein, rat
  • Grem2 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • NBL1 protein, Xenopus
  • NBL1 protein, human
  • Plant Proteins
  • Proteins
  • Transforming Growth Factor beta
  • Xenopus Proteins
  • bmp4 protein, Xenopus
  • cer1 protein, Xenopus