Further Development 12.5: The PMZ Is Equivalent to the Amphibian Nieuwkoop Center

Birds and Mammals

It now seems apparent that the PMZ contains cells that act as the equivalent of the amphibian Nieuwkoop center. When placed in the anterior region of the marginal zone, a graft of PMZ tissue (posterior to and including Koller’s sickle) is able to induce a primitive streak and Hensen’s node without contributing cells to either structure (Bachvarova et al. 1998; Khaner 1998). Current evidence suggests that the entire marginal zone produces Wnt8c (capable of inducing the accumulation of β-catenin) and that, like the amphibian Nieuwkoop center, the PMZ cells secrete Vg1, a member of the TGF-β family (Mitrani et al. 1990; Hume and Dodd 1993; Seleiro et al. 1996).

Wnt8c and Vg1 act together to induce expression of Nodal (another secreted TGF-β protein) in the future embryonic epiblast next to Koller’s sickle and the PMZ (Skromne and Stern 2002). Thus, the pattern appears similar to that of amphibian embryos. Recent studies suggest that Nodal activity is needed to initiate the primitive streak, and that it is the secretion of Cerberus—an antagonist of Nodal—by the primary hypoblast cells that prevents primitive streak formation (Bertocchini et al. 2004; Voiculescu et al. 2014). As the primary hypoblast cells move away from the PMZ, Cerberus protein is no longer present, allowing Nodal activity (and therefore formation of the primitive streak) in the posterior epiblast. Once formed, however, the streak secretes its own Nodal antagonist—the Lefty protein—thereby preventing any further primitive streaks from forming. Eventually, the Cerberus-secreting hypoblast cells are pushed to the future anterior of the embryo, where they contribute to ensuring that neural cells in this region become forebrain rather than more posterior structures of the nervous system. 1

1 Conjoined twins may be formed by having two sources of Nodal expression within the same blastodisc. Experimentation with chick embryos can produce two axes in the same blastodisc by circumventing the usual inhibition of Nodal by the Vg1-secreting posterior cells (Bertocchini et al. 2004). In mammals, multiple axes can also form if Nodal antagonists are blocked (Perea-Gomez et al. 2002). Of course if we are considering an armadillo, then it normally develops four independent primitive streaks within the same blastoderm, producing (quite late in development) four monozygotic twins. The timing of this ability has informed the “14-day rule” for which research can be done on human embryos in some countries.

Literature Cited

Bachvarova, R. F., I. Skromne and C. D. Stern. 1998. Induction of primitive streak and Hensen’s node by the posterior marginal zone in the early chick embryo.Development125: 3521–3534.
PubMed Link

Bertocchini, F., I. Skromne, L. Wolpert and C. D. Stern. 2004. Determination of embryonic polarity in a regulative system: Evidence for endogenous inhibitors acting sequentially during primitive streak formation in the chick embryo.Development131: 3381–3390.
PubMed Link

Khaner, O. 1998. The ability to initiate an axis in the avian blastula is concentrated mainly at a posterior site.Dev. Biol.194: 257–266.
PubMed Link

Hume, C. R. and J. Dodd. 1993.Cwnt-8C:A novel Wnt gene with a potential role in primitive streak formation and hindbrain organization.Development119: 1147–1160.
PubMed Link

Mitrani, E., T. Ziv, G. Thomsen, Y. Shimoni, D. A. Melton and A. Bril. 1990. Activin can induce the formation of axial structures and is expressed in the hypoblast of the chick.Cell63: 495–501.
PubMed Link

Seleiro, E. A. P., D. J. Connolly and J. Cooke. 1996. Early developmental expression and experimental axis determination by the chickenVg1gene.Curr. Biol.6: 1476–1486.
PubMed Link

Skromne, I. and C. D. Stern. 2002. A hierarchy of gene expression accompanying induction of the primitive streak by Vg1 in the chick embryo.Mech. Dev.114: 115–118.
PubMed Link

Voiculescu, O., L. Bodenstein, I. J. Lau and C. D. Stern. 2014. Local cell interactions and self-amplifying individual cell ingression drive amniote gastrulation.Elife21;3:e01817.
PubMed Link

All the material on this website is protected by copyright. It may not be reproduced in any form without permission from the copyright holder.