The “organizer” of the chick embryo forms from cells initially located just anterior to the posterior marginal zone. The epiblast and middle layer cells in the anterior portion of Koller’s sickle become Hensen’s node, as described earlier. The posterior portions of Koller’s sickle contribute to the posterior portion of the primitive streak (Figure 1). Hensen’s node has long been known to be the avian equivalent of the amphibian dorsal blastopore lip, since (1) it is the region whose cells become the prechordal plate and chordamesoderm, (2) it is the region whose cells can both induce and pattern a second embryonic axis when transplanted into other locations of the gastrula (Figure 2; Waddington 1933,1934; Gallera 1966; Nicolet 1970), and (3) it expresses the same marker genes as Spemann’s organizer in amphibians and the embryonic shield of teleost fishes, such as the transcription factor Goosecoid (Izpisua-Belmonte et al. 1993). Moreover, Hensen’s node can induce neural tissue when grafted into fish, amphibian, or mammalian embryos (Waddington 1936; Kintner and Dodd 1991; Hatta and Takahashi 1996).
As is the case in all vertebrates, the dorsal mesoderm is able to induce the formation of the central nervous system in the ectoderm overlying it. The cells of Hensen’s node and its derivatives act like the amphibian organizer, and they secrete BMP inhibitors such as Chordin, Noggin, and Nodal. These proteins repress BMP signaling and dorsalize the ectoderm and mesoderm (Figure 3). However, repression of BMP signals by these antagonists does not appear to be sufficient for neural induction (see Stern 2005b). Fibroblast growth factors synthesized in the hypoblast and in Hensen’s node precursor cells just prior to gastrulation appear to be critical for preparing the epiblast to generate neuronal phenotypes. FGFs can block BMP signaling, but this fact alone does not account for the ability of FGFs to induce a transient expression of pre-neural genes in the epiblast (Streit et al. 1998, 2000). These neural genes do not stay active unless they are supported by BMP antagonists (Streit et al. 1998, 2000; Albazerchi and Stern 2006). Thus, FGF signaling inhibits BMPs from inducing the genes that specify ectoderm to become epidermis, and they activate the genes that specify ectoderm to become neural.
Indeed, fibroblast growth factors play four fundamental roles in cell specification during gastrulation:
Thus, FGFs appear to be critically important regulators of cell fate in the early chick embryo (Streit et al. 2000; Sheng et al. 2003; Albazerchi and Stern 2006).
While they are still in the epiblast, but close to the primitive streak, the mesoderm cells appear to receive instructions that tell them exactly where they are along the anterior-posterior axis. The entire length of the notochord at the midline is derived from cells that are present in Hensen’s node by the full primitive streak stage. A population of progenitor cells remains in the node; their descendants gradually leave as the node regresses, laying down the chordamesoderm and the ventral midline of the neural tube (the future floor plate of the spinal cord) (Selleck and Stern 1991; Psychoyos and Stern 1996; Tzouanacou et al. 2009). Therefore, anterior-posterior identities along the axis from the hindbrain to the tail are specified as a function of the time of emergence from the primitive streak and Hensen’s node.
It has been proposed that the length of time cells are resident in the primitive streak region determines which Hox genes are expressed by the cells. This pattern of Hox gene expression can also be under the influence of the FGF and retinoic acid gradients (Gaunt 1991; Wilson et al. 2009). As we will detail later in the chapter, Hox genes are the vertebrate homologues of the homeotic (Hom-C) genes of Drosophila. And just as in Drosophila embryos, vertebrate Hox genes specify the identity of cells along the anterior-posterior axis. In the case of vertebrates, however, there are four gene clusters (HoxA, HoxB, HoxC, and HoxD) instead of just one, and rather than individual Hox genes appearing at particular segmental levels, there is a nested set of Hox gene expression. For example, the mesodermal precursor cells are patterned along the anterior-posterior axis by the HoxB genes, which appear to inform the cells when to leave the epiblast and ingress into the primitive streak. “Anterior” Hox genes (which are identified with lower numbers, e.g., Hoxb4) are expressed early and extend farther anterior than genes such as Hoxb9, which is expressed later and does not extend as far into the embryo’s anterior (Iimura and Pourquié 2006; Figure 5). Thus, the more posterior cells express more Hox genes than the more anterior cells do.
Albazerchi, A. and C. D. Stern. 2007. A role for the hypoblast (AVE) in the initiation of neural induction, independent of its ability to position the primitive streak. Dev. Biol. 301: 489–503.
PubMed Link
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. Development 125: 3521–3534.
PubMed Link
Faure, S., P. de Santa Barbara, D. J. Roberts and M. Whitman. 2002. Endogenous patterns of BMP signaling during early chick development. Dev. Biol. 244: 44–65.
PubMed Link
Gallera, J. 1966. Le pouvoir inducteur de la chorde et du mesoblaste parachordal chez les oiseaux en fonction du facteur ‘temps’. Acta Anat. (Basel) 63: 388–397.
Gaunt, S. J. 1991.Expression patterns of mouse Hox genes: Clues to an understanding of developmental and evolutionary strategies.Bioessays 13: 505–513.
PubMed Link
Hatta, K. and Y. Takahashi. 1996. Secondary axis induction by heterospecific organizers in zebrafish. Dev. Dyn. 205: 183–195.
PubMed Link
Iimura, T. and O. Pourquié. 2006. Collinear activation of Hoxb genes during gastrulation is linked to mesoderm cell ingression. Nature 442: 568–571.
PubMed Link
Izpis˙a-Belmonte, J. C., E. M. De Robertis, K. G. Storey and C. D. Stern. 1993. The homeobox gene goosecoid and the origin of organizer cells in the early chick blastoderm. Cell 74: 645–659.
PubMed Link
Kintner, C. R. and J. Dodd. 1991. Hensen's node induces neural tissue in Xenopus ectoderm. Implications for the action of the organizer in neural induction. Development 113: 1495–1505.
PubMed Link
Nicolet, G. 1970. Analyse autoradiographique de la localisation des differentes ebauches presomptives dans la ligne primitive de l'embryon de Poulet. Embryol. Exp. Morph. 23: 79–108.
Selleck, M. A. J. and C. D. Stern. 1991. Fate mapping and cell lineage analysis of Hesen’s node in the chick embryo. Development 112: 615–626.
PubMed Link
Psychoyos, D. and C. D. Stern. 1996. Fates and migratory routes of primitive streak cells in the chick embryo. Development 122: 1523–1534.
PubMed Link
Sheng, G., M. dos Reis and C. D. Stern. 2003. Churchill, a zinc finger transcriptional activator, regulates the transition between gastrulation and neurulation. Cell 115: 603–613.
PubMed Link
Stern, C. D. 2005b. Neural induction: Old problems, new findings, yet more questions. Development 132: 2007–2021.
PubMed Link
Streit , A., A. J. Berliner, C. Papanayotou, A. Sirulnik and C. D. Stern. 2000. Initiation of neural induction by FGF signalling before gastrulation. Nature 406: 74–78.
PubMed Link
Streit , A., K. J. Lee, I. Woo, C. Roberts, T. M. Jessell and C. D. Stern.1998. Chordin regulates primitive streak development and the stability of induced neural cells, but is not sufficient for neural induction in the chick embryo. Development 125: 507–519.
PubMed Link
Tzouanacou, E., A. Wegener, F. J. Wymeersch, V. Wilson and J. F. Nicolas. 2009. Redefining the progression of lineage segregations during mammalian embryogenesis by clonal analysis. Dev. Cell 17: 365–376.
PubMed Link
Waddington, C. H. 1933. Induction by the primitive streak and its derivatives in the chick. J. Exp. Zool. 10: 38–46.
Waddington, C. H. 1934. Experiments on embryonic induction. II. Experiments on coagulated organisers in the chick. Exp. Biol. 11: 218–223.
Waddignton 1936
Wilson, V., I Olivera-Martinez and K. G. Storey. 2009. Stem cells, signals, and vertebrate body axis extension. Development 136: 1591–1604.
PubMed Link