<P> Nodal, a known mesodermal inducer of the TGFB superfamily, has been implicated in streak formation . Mouse embryos mutant for Nodal fail to gastrulate and lack most mesoderm, but more than playing a role in mesoderm induction, Nodal regulates the induction and / or maintenance of the primitive streak . In the presence of hypoblast, Nodal is unable to induce ectopic streaks in the chick embryo, while its removal, induces expression of Nodal, Chordin and Brachyury, suggesting that the hypoblast must have a certain inhibitory effect on Nodal signaling . Indeed, the multifunctional antagonist of Nodal, Wnt and BMP signaling, Cerberus (produced in the hypoblast) and Cerberus - Short (which inhibits only Nodal), through its effect on Nodal signaling, inhibits streak formation . Eventually, the hypoblast gets displaced anteriorly by the moving endoblast, allowing streak formation at the posterior end . At the anterior end, the presence of the hypoblast and the antagonists it secretes, such as Cerberus, inhibit the expression of Nodal and hence restrict streak formation to the posterior end only . Similarly to the hypoblast in chick, the AVE in the mouse secretes two antagonists of Nodal signaling, Cerberus - like, Cerl, and Lefty1 . In mouse, Cer - / -; Lefty1 - / - double mutants develop multiple streaks as indicated by ectopic expression of Brachyury and can be partially rescued by the removal of one copy of the Nodal gene . In the mouse, the AVE restricts streak formation through the redundant functions of Cer1 and Lefty1, which negatively regulate Nodal signaling . The role of the mouse's AVE in ensuring the formation of a single primitive streak is evolutionarily conserved in the hypoblast of the chick . </P> <P> Another important pathway in modulating formation of the primitive streak is FGF, which is thought to work together with Nodal to regulate this process . Inhibition of FGF signaling through expression of a dominant negative receptor, using a FGF receptor inhibitor (SU5402) or depletion of FGF ligands, inhibit mesoderm formation and this in turn, inhibits streak formation . Furthermore, ectopic streak formation induced by Vg1 required FGF signaling . </P> <P> Finally, BMP signaling is also important for regulating the process of streak formation in the chick embryo . The site of streak formation is characterized by low BMP signals, while the rest of the epiblast displays high levels of BMP activation . In addition, misexpression of either BMP4 or BMP7 prevents streak formation, while the BMP inhibitor Chordin induces ectopic streak formation in the chick, suggesting that streak formation is likely to require BMP inhibition . </P> <P> The primitive streak is an important concept in bioethics, where some experts have argued that experimentation with human embryos is permissible, but only before the primitive streak develops, generally around the fourteenth day of existence . The development of the primitive streak is taken, by such bioethicists, to signify the creation of a unique, human being . In some countries, it is illegal to develop a human embryo for more than 14 days outside a woman's body . </P>

When does the primitive streak form in the embryo