The primitive streak is one of the most important, yet enigmatic, structures of amniote species. The streak establishes the anteroposterior embryonic body axis, and provides a conduit through which embryonic mesoderm and endoderm are formed. Whilst the streak's anterior end, called the node, has been the subject of countless investigations over the past decades, the whereabouts of the posterior primitive streak have not been satisfactorily identified in any species.

Using a combination of classical methods of experimental embryology in living embryos, genetics, and protein localization, we have discovered that the primitive streak's posterior limit is not confined to the embryo proper. Rather, contrary to conventional wisdom, it extends into the extraembryonic region. There, it establishes both the allantois, or umbilical component of the chorio-allantoic placenta, and a self-contained cell reservoir that bears the hallmarks of a stem cell niche. This niche, called the "allantoic core domain" (ACD), is essential for allantoic elongation to the chorion to ensure placentation. In addition, a variety of allantoic and embryonic cell types, including the primordial germ cells, may be specified and deployed from it. By contrast, the intraembryonic posterior component of the primitive streak contributes cells to the allantoic cell surface which, over time, extend to the embryonic body wall and gut.

We propose that defects in the posterior primitive streak's components, and/or the structures established by them, lead to a spectrum of umbilical-associated embryonic birth defects which fall into the category of "orphan" diseases, as their underlying etiologies are largely unknown. Many of these involve the embryonic midline, and include the caudal body wall, gastrointestinal and reproductive systems. Our immediate goals are to elucidate the properties of the posterior primitive streak, and the cells deployed by the ACD. Our long term goals are to discover the steps by which the streak provides the developmental link between the embryo and its umbilical cord, thereby ensuring a proper fetal/maternal relationship.

Select Publications

Downs, K.M. (2009). Invited Peer-Reviewed Hypothesis: The enigmatic primitive streak: Prevailing notions and challenges concerning the embryonic body axis. BioEssays 31, 892-902.

Downs, K.M., Inman, K.E., Jin, D.X., and Enders, A.C.,(2009). The Allontoic Core Domain (ACD): New insights into development of the murine allantois and its relation to the primitive streak. Dev. Dyn. 238, 523-553.

Downs, K.M. (2008). Controversies in Science: Embryological Origins of the Human Individual. DNA and Cell Biol. 27, 3-7 ( reprinted excerpts from Downs, 2008, In Controversies in Science and Technology).

Downs, K.M. (2008) Systematic localization of Oct-3/4 (Pou5f1) to the gastrulating mouse conceptus suggests manifold roles of Oct-3/4 in mammalian development. Dev.Dyn., 237, 464-474.

Inman, K.E. and Downs, K.M. (2007). Invited Review: The murine allantois: emerging paradigms in formation and development of the mammalian umbilical cord and its relation to the fetus. Genesis 45, 237-258.

Inman, K.E. and Downs, K.M. (2006). Spatiotemporal localization of Brachyury (T) in the embryonic and extraembryonic tissues of the mouse gastrula. Gene Exp. Patterns, 6,788-793.

Inman, K.E. and Downs, K.M. (2006) Brachyury is required for elongation and vasculogenesis in the murine allantois. Development, 133, 2947-2959.

Ziegler, B.M., Sugiyama, D., Chen, M., Guo, Y., Downs, K.M., and Speck, N.A. (co-corresponding authors) (2006). The allantois and chorion, isolated before circulation or chorio-allantoic fusion, have hemtopoietic potential. Development 133, 4183-4192 (Featured in "In This Issue")

Uy, G.D., Downs, K.M., and Gardner, R.L. (2002). Inhibition of trophoblast stem cell potential in chorionic ectoderm coincides with occlusion of the ectoplacental cavity in the mouse. Development, 129, 3913-3924.