The Downs Laboratory
Faculty > Karen M. Downs
Karen M. Downs
Professor, Anatomy
kdowns@wisc.edu
Organ System/Disease Focus
Umbilical cord; vasculogenesis; placentation
Aligned Research Focus
Stem cell reservoir in the allantois and its role in building the umbilical vasculature and aligning it with the fetus and placenta
Research Description
Precisely aligned between the fetal and maternal circulatory systems, the murine allantois will become the umbilical component of the chorio-allantoic placenta. The allantois is generated in part by extrinsic mechanisms involving the primitive streak. However, studies from our laboratory suggest that intrinsic allantois-derived mechanisms are also involved.
We report the presence of a new architectural and functional component of the murine allantois, here named the Allantoic Core Domain, or ACD, recently identified by Brachyury (T). The ACD fulfills our expectations of an intrinsic organizing center. The ACD occupies a discrete space within the base of the allantois, it is continuous with but functionally distinct from the posterior embryonic portion of the primitive streak, and the ACD persists throughout the period of allantoic elongation and vasculogenesis. If ablated, the ACD does not reform. Classical experiments in living mouse gastrulae revealed that the ACD generates a self-renewing population of Oct-3/4-positive cells distinct from the germ line. Drawing from this reservoir, the ACD sends forth a PECAM-positive projection that organizes the primary umbilical vasculature in correct alignment with the embryonic A-P axis.
Further data suggest that the ACD is involved in formation of the hindgut. On the basis of these novel findings, we suggest that the terminus of the posterior streak, heretofore poorly defined, lies within the base of the allantois where its activity unifies the embryonic and extraembryonic compartments of the mammalian conceptus, ensuring an optimally functioning vascular continuum between the fetus and its mother.
Selected References
Uy GD, Downs KM, Gardner R.L. Inhibition of trophoblast stem cell potential in chorionic ectoderm coincides with occlusion of the ectoplacental cavity in the mouse. Development 129:3913-3924. 2002.
Inman KE, Downs KM. Brachyury is required for elongation and vasculogenesis in the murine allantois.. Development 133:2947-2959. 2006.
Ziegler BM, Sugiyama D, Chen M, Guo Y, Downs KM, Speck NA. (co-corresponding authors). The allantois and chorion, isolated before circulation or chorio-allantoic fusion, have hematopoietic potential. Development 133:4183-4192. 2006.