Our long term goal is to understand the signals that pattern the early vertebrate embryo, and particularly the role that BMP antagonists play in this process. We study this problem in both amphibians and mice, since each offers different experimental advantages. Xenopus laevis produces large numbers of eggs that are readily manipulated by injection and microsurgery. The combination of experimental embryology and molecular manipulation provide the tools to understand embryonic signaling at the molecular level. We also complement use of X. laevis with use of X. tropicalis, which offers the advantages of diploidy and a sequenced genome, both advantages for manipulating gene expression by Morpholino oligonucleotide-mediated knockdowns. Our work in the mouse has taken advantage of targeted mutations. The phenotypes of these mutations have suggested particular developmental contexts where BMP antagonists are crucial, and some of these contexts are particularly relevant to human developmental disorders. In the next grant period we will study how BMP antagonists implement important developmental decisions, either singly, or in overlapping combinations. These include the maintenance of neural stem cell populations and skeletal patterning in noggin mutants, and the induction and maintenance of somite differentiation in noggin/gremlin double mutants. Finally we will study the contribution of different BMP antagonists to formation of the dorsal ventral, and anterior posterior axes in the early embryo.
| Young, John J; Kjolby, Rachel A S; Wu, Gloria et al. (2017) Noggin is required for first pharyngeal arch differentiation in the frog Xenopus tropicalis. Dev Biol 426:245-254 |
| Stafford, David A; Dichmann, Darwin S; Chang, Jessica K et al. (2017) Deletion of the sclerotome-enriched lncRNA PEAT augments ribosomal protein expression. Proc Natl Acad Sci U S A 114:101-106 |
| Ray, Ayan; Singh, Pratik Narendra Pratap; Sohaskey, Michael L et al. (2015) Precise spatial restriction of BMP signaling is essential for articular cartilage differentiation. Development 142:1169-79 |
| Stafford, David A; Monica, Stefanie D; Harland, Richard M (2014) Follistatin interacts with Noggin in the development of the axial skeleton. Mech Dev 131:78-85 |
| Canalis, Ernesto; Brunet, Lisa J; Parker, Kristen et al. (2012) Conditional inactivation of noggin in the postnatal skeleton causes osteopenia. Endocrinology 153:1616-26 |
| Stafford, David A; Brunet, Lisa J; Khokha, Mustafa K et al. (2011) Cooperative activity of noggin and gremlin 1 in axial skeleton development. Development 138:1005-14 |
| Harland, Richard M; Grainger, Robert M (2011) Xenopus research: metamorphosed by genetics and genomics. Trends Genet 27:507-15 |
| Wills, Andrea E; Choi, Vivian M; Bennett, Margaux J et al. (2010) BMP antagonists and FGF signaling contribute to different domains of the neural plate in Xenopus. Dev Biol 337:335-50 |
| Sohaskey, Michael L; Jiang, Yebin; Zhao, Jenny J et al. (2010) Osteopotentia regulates osteoblast maturation, bone formation, and skeletal integrity in mice. J Cell Biol 189:511-25 |
| Sohaskey, Michael L; Yu, Jane; Diaz, Michael A et al. (2008) JAWS coordinates chondrogenesis and synovial joint positioning. Development 135:2215-20 |
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