The broad objectives of this study are to understand the mechanisms that govern mammalian gastrulation, especially the growth, differentiation and movement of the mesoderm germ layer in the mouse embryo. To achieve this goal a phenotypic and molecular characterization will be performed on two mutants isolated by the Anderson lab in a genetic screen for mutations affecting mouse embryogenesis. These recessive mutants, named U4 and wing-shaped neural plate (wsnp), both exhibit severe abnormalities in the formation and morphogenesis of the mesoderm germ layer. These mutant embryos are reminiscent of embryos that lack the extracellular matrix protein fibronectin, suggesting that the U4 and wsnp genes affect either the adoption of mesodermal fate or the migration of mesodermal cells. The functions of U4 and wsnp will be analyzed by using marker gene expression to determine the identity and location of mesodermal tissues in mutant embryos, in comparison to fibronectin mutants. Cell-autonomous requirements for U4 and wsnp will be tested by creating and analyzing mutant/wild-type chimeras. Cell migration assays will be performed in vitro to test whether U4 and wsnp are required for motility. The U4 and wsnp genes will be molecularly mapped and identified; as the DNA sequences of the U4 and wsnp are determined, their expression patterns will be assayed, and their biochemical functions will be determined. The functional characterization of U4 and wsnp will provide insights into the genetic control of cell movement, a process implicated in many human diseases, including metastatic cancer.
| Quas, Jodi A; Yim, Ilona S; Oberlander, Tim F et al. (2014) The symphonic structure of childhood stress reactivity: patterns of sympathetic, parasympathetic, and adrenocortical responses to psychological challenge. Dev Psychopathol 26:963-82 |
