BMP2 in the visceral endoderm directs anterior morphogenesis during mouse gastrulation

Embryonic development is characterized by coordinated growth, differentiation and morphogenesis. Morphogenesis --the generation of shape- is most evident during gastrulation, when extensive tissue rearrangements accompany cell proliferation and lineage specification to establish the embryonic body plan. Proper development and patterning in the early mouse gastrula depend on reciprocal interactions between the epiblast and two surrounding extra-embryonic tissue layers: extra-embryonic ectoderm and visceral endoderm (VE.) Recent lineage analysis has shown that the visceral endoderm is not solely an extraembryonic lineage but also a component of developing gut endoderm. My studies on BMP2 signaling in the mouse gastrula indicate that beyond its lineage contribution to embryonic endoderm, the VE also functions in gut tube morphogenesis.;The series of experiments presented in this thesis identify a VE-derived signal that directs morphogenesis of the developing gut endoderm; moreover they implicate endodermal movement as a driving force for placement of the head and heart. Bmp2 is expressed in the VE lineage throughout gastrulation and in epiblast derived extra-embryonic and cardiac mesoderm as well. Mutants die at midgestation and show morphogenetic defects in head, heart, and extraembryonic mesoderm. Considering Bmp2 expression in both epiblast and VE lineages, I asked whether this phenotype reflected loss of Bmp2 in the VE and/or epiblast lineages. Using epiblast and VE tissue specific gene ablation I uncovered unique and complementary roles for BMP2 in each lineage. I conclude that BMP2 in epiblast derivatives mediates closure and positioning of the amnion, while BMP2 in the VE lineage functions to direct foregut invagination, thus coordinating proper placement of head and heart. Together with the phenotype of the epiblast specific knockout of Bmpr1a, these findings potentially identify a signaling cascade wherein BMP2 in the visceral endoderm signals to its receptor in the epiblast to direct anterior morphogenesis during mouse gastrulation.