Primitive streak

The primitive streak is a structure that forms in the blastula during the early stages of avian, reptilian and mammalian embryonic development. It forms on the dorsal (back) face of the developing embryo, toward the caudal or posterior end.Human embryo—length, 2 mm. Dorsal view, with the amnion laid open. X 30.Lateral section through the mammalian blastodisc. The primitive streak is a structure that forms in the blastula during the early stages of avian, reptilian and mammalian embryonic development. It forms on the dorsal (back) face of the developing embryo, toward the caudal or posterior end. The presence of the primitive streak will establish bilateral symmetry, determine the site of gastrulation and initiate germ layer formation. To form the streak, reptiles, birds and mammals arrange mesenchymal cells along the prospective midline, establishing the second embryonic axis, as well as the place where cells will ingress and migrate during the process of gastrulation and germ layer formation.The primitive streak extends through this midline and creates the left–right and cranial–caudal body axes, and marks the beginning of gastrulation. This process involves the ingression of mesoderm progenitors and their migration to their ultimate position, where they will differentiate into the mesoderm germ layer that, together with endoderm and ectoderm germ layers, will give rise to all the tissues of the adult organism. Given that the chicken embryo can be easily manipulated, most of our knowledge about the primitive streak comes from avian studies. The marginal zone of a chick embryo contains cells that will contribute to the streak. This region has a defined anterior-to-posterior gradient in its ability to induce the primitive streak, with the posterior end having the highest potential. The epiblast, a single epithelial layer blastodisc, is the source of all embryonic material in amniotes and some of its cells will give rise to the primitive streak. All cells in the epiblast can respond to signals from the marginal zone, but once a given region is induced by these signals and undergoes streak formation, the remaining cells in the epiblast are no longer responsive to these inductive signals and prevent the formation of another streak. Underlying the epiblast is the hypoblast, where the extra-embryonic tissue originates. In the chick, the absence of the hypoblast results in multiple streaks, suggesting that its presence is important for regulating the formation of a single primitive streak. In mice, this structure is known as the Anterior Visceral Endoderm (AVE). The formation of the primitive streak in the blastocyst involves the coordinated movement and re-arrangement of cells in the epiblast. Even before the streak is visible, epiblast cells have started to move. Two counter-rotating flows of cells meet at the posterior end, where the streak forms. There is little movement in the center of these flows, while the greatest movement is observed at the periphery of the vortices. The Polonaise Movement is key for the formation of the primitive streak. Cells overlaying Koller’s Sickle in the posterior end of the chick embryo move towards the midline, meet and change direction towards the center of the epiblast. Cells from the lateral posterior marginal zone replace those cells that left Koller’s Sickle by meeting at the center of this region, changing direction and extending anteriorly. As these cells move and concentrate at the posterior end of the embryo, the streak undergoes a single- to multi-layered epithelial sheet transition that makes it a macroscopically visible structure. Several mechanisms, including oriented cell division, cell-cell intercalation and chemotactic cell movement, have been proposed to explain the nature of the cellular movements required to form the primitive streak. The formation of the primitive streak relies on a complex network of signaling pathways that work together to ensure that this process is highly regulated. Activation of various secreted factors (Vg1, Nodal, Wnt8C, FGF8 and Chordin) and transcription factors (Brachyury and Goosecoid) adjacent to the site of streak formation is required for this process.In addition, structures such as the hypoblast also play an important role in the regulation of streak formation. Removal of the hypoblast in the chick results in correctly patterned ectopic streaks, suggesting that the hypoblast serves to inhibit formation of the primitive streak. Similarly, Vg1 (a TGFB family member) misexpression and grafts of the posterior marginal zone in chicks can also induce ectopic streaks, but only within the marginal zone of the embryo, indicating a specific characteristic of this region in its ability to induce streak formation. Several lines of evidence point to Wnt expression as the determinant of this ability. Deletion of Wnt3 in mouse embryos results in the absence of a streak formation, similarly to the phenotype of B-catenin mutant embryos. In addition, mutating the intracellular negative regulator of Wnt signaling, Axin, and misexpression of the chick cWnt8C produces multiple streaks in mouse embryos. Localization of Wnt and components of its pathway, Lef1 and B-catenin, further supports streak-inducing role in the marginal zone. Furthermore, it is expressed as a gradient decreasing from posterior to anterior, corresponding to the streak-inducing ability of the marginal zone. Misexpression of Vg1 or Wnt1 alone failed to induce an ectopic streak in the chick, but together their misexpression resulted in ectopic streak formation, confirming that the streak-inducing ability of the posterior marginal zone could be attributed to Wnt signaling and that Vg1 and Wnt must cooperate to induce this process. Misexpression of Vg1 along with Wnt antagonists, Crescent or Dkk-1, prevents the formation of ectopic streaks, demonstrating the importance of Wnt activity in the formation of Vg1-induced ectopic streaks and hence its implication in normal primitive streak formation. Any given slice from the blastoderm is able to generate a complete axis until the time of gastrulation and primitive streak formation. This ability to generate a streak from the pre-streak stage chick embryo indicates that there must be a mechanism to ensure that only a single streak forms. The hypoblast secretes an antagonist of Nodal that prevents ectopic streak formation in the chick.