Mutation and analysis of Dan, the founding member of the Dan family of transforming growth factor beta antagonists.
The Dan family of transforming growth factor beta antagonists is a large, evolutionarily conserved family of proteins. Little is known about either the specificity of these antagonists or the biological roles of these proteins. We have characterized Dan, the founding member of this family, with regard to both its biochemical specificity and its biological roles. Although DAN is not an efficient antagonist of BMP-2/4 class signals, we found that DAN was able to interact with GDF-5 in a frog embryo assay, suggesting that DAN may regulate signaling by the GDF-5/6/7 class of BMPs in vivo. Intriguingly, in developing neurons, Dan mRNA was localized to axons, suggesting a potential role for the DAN protein in axonal outgrowth or guidance. Mice lacking Dan activity were generated by gene targeting and displayed subtle, background-dependent defects.
Dionne
M S
MS
Division of Genetics and Development, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Skarnes
W C
WC
Harland
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors; D001842:Bone and Bones / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D018390:Gene Targeting; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008845:Microinjections; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000002:abnormalities / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000002:abnormalities / Q000196:embryology / Q000235:genetics
D019485:Bone Morphogenetic Proteins; D016207:Cytokines; C525894:Gdf5 protein, mouse; C490088:Grem2 protein, mouse; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; C490085:NBL1 protein, Xenopus; D011506:Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins