title: The mammalian twisted gastrulation gene functions in foregut and craniofacial development.
abstract: Extracellular modulators of cell-cell signaling control numerous aspects of organismal development. The Twisted gastrulation (Twsg1) gene product is a small, secreted cysteine-rich protein that has the unusual property of being able to either enhance or inhibit signaling by the bone morphogenetic protein (BMP) subfamily of TGF-beta type factors in a context-dependent manner. In this report, we characterize the early embryonic and skeletal phenotypes associated with loss of Twsg1 function in mice. All Twsg1 mutant mice, irrespective of genetic background, exhibit deletions of neural arches in the cervical vertebrae. In a C57BL/6 background, we also observe pronounced forebrain defects including rostral truncations, holoprosencephaly, cyclopia, as well as alterations in the first branchial arch (BA1) leading to lack of jaw (agnathia). Characterization of marker expression suggests that these defects are attributable to loss of signaling from forebrain-organizing centers including Fgf8 from the anterior neural ridge (ANR) and Shh from the prechordal plate (PrCP). In addition, we find defects in the foregut endoderm and a reduction in Hex expression, which may contribute to both the forebrain and BA1 defects.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710-3709, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Petryk
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Anderson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jarcho
authors.forename: Irina
authors.initials: I
authors.lastname: Leaf
authors.forename: Cathy S
authors.initials: CS
authors.lastname: Carlson
authors.forename: John
authors.initials: J
authors.lastname: Klingensmith
authors.forename: William
authors.initials: W
authors.lastname: Shawlot
authors.forename: Michael B
authors.initials: MB
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001921:Brain / Q000196:embryology*; D019465:Craniofacial Abnormalities / Q000196:embryology* / Q000235:genetics; D003433:Crosses, Genetic; D017931:DNA Primers; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D006652:Histological Techniques; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D041742:Upper Gastrointestinal Tract / Q000196:embryology*
chemical_list: D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D053823:Hedgehog Proteins; D011506:Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators; C473561:twisted gastrulation protein, mouse