The Developmental Hourglass
In 1828, Karl Ernst von Baer published his detailed observations of vertebrate embryos, along with important generalizations that became known as Baer’s “law of embryology. These were discussed in Chapter 1. Namely:
- The more general characters of a large group of animals appear earlier in their embryos than the more special characters.
- From the most general forms the less general are developed, and so on, until finally the most special arise.
- Every embryo of a given animal form, instead of passing through the other forms, becomes separate from them.
- Fundamentally, therefore, the embryo of a higher form never resembles any other form, but only its embryo.
Thus, one might have the picture of all vertebrates starting from the same place—something like a late neurula, with the landmarks of neural tube, notochord, and somite each present and on the same orientation, and then diverging into their particular mammal-specific, bird-specific, or amphibian-specific trajectories. This would be correct once that stage was achieved. But von Baer (1886) also recognized that the needs of reproduction (in the sea, on land, within a mother) produced many varieties of egg types and cleavages*. Thus, he writes in his Autobiography about cleavage stage frog embryos:
“Only after these preparations for future developments are concluded does the typical vertebrate development set in: the rising of two ridges which are, at the beginning, so distant from each other that one hardly dares to see them in the two halves of the back, but which approach one another, attesting to what they in fact.”
Thus, there appears to be a great deal of variation in the beginning of development (cleavage and gastrulation), but around the time of neurulation, this variation gets minimalized, and after a period of time when all vertebrate embryos look very much alike, they diverge again. This has been called the developmental “hourglass.” (Sander 1983; Duboule 1994; Raff 1996). Sander (1983) and Raff (1996) have argued that during this middle portion—the phylotypic stage, the stage that typifies a phylum—there are developmental constraints that work against variation. For instance, the late neurula, also known as the pharyngula, is the phylotypic stage that appears to be critical for all vertebrates (Figure 1; Slack et al. 1993).
The causes for this constriction in the center of the hourglass may come from developmental constraints. Before the vertebrate pharyngula stage there are few inductive events, and most of them are on global scales (involving axis specification). In these early stages of development there is a great deal of regulation, so small changes in morphogen distributions or the position of cleavage planes can be accommodated (Henry et al. 1989). After the pharyngula stage there are a great many inductive events, but almost all of them occur within discrete modules (Figure 2). The lens induces the cornea, but if it fails to do so, only the eye is affected. But during the phylotypic pharyngula stage the modules interact. Failure to have the heart in a certain place can affect the induction of eyes. Failure to induce the mesoderm in a certain region leads to malformations of the kidneys, limbs, and tail. By searching the literature on congenital anomalies, Galis and Metz (2001) have documented that the pharyngula is much more vulnerable than any other stage. Moreover, based on patterns of multiple organ anomalies in the same person, they concluded that the multiple malformations were due to the interactivity of the modules at this stage. Thus, this phylotypic stage that typifies the vertebrate phylum appears to constrain its evolution. Once an organism becomes a vertebrate, it is probably impossible for it to evolve into anything else.
The notion of a phylogenetic stage has been supported by molecular evidence. Some of the first evidence (Duboule 1994) came from Hox gene expression patterns. More recently, the expression of entire genomes have been surveyed (Domazet-Lošo and Tautz 2010; Kalinka et al. 2010; Irie et al. 2011; Wang et al. 2013), and these have shown that (1) the gene expression patterns within a phylum show hourglass-like divergence, and (2) the stages showing the highest similarity are those from the late pharyngula in vertebrates, and segmentation period in Drosophila species. Not only expressions, but also regulatory regions were reported to be conserved in the phylotypic period (Piasecka et al. 2013). Indeed, Piasecka and colleagues (2013) have recently concluded that the genes following the hourglass pattern are largely those having evolutionarily conserved regulatory regions.
Therefore, after a preliminary period of cleavage and gastrulation that can vary greatly between members of a phylum (think of chicks, mammals, and frogs), there is a phylotypic period (in vertebrates, the late neurula/phayngula) where a series of interactions takes place between modules, which creates great constraint. After that stage, there can be great variation again, as selection for specific niches takes over. Fish make gills, reptiles make jaws, mammals make ear bones.
* von Baer also knew that heterochronic changes would prevent the embryos from being identical, even in this phylotypic stage. His Autobiography continues, “Altogether, the development of frogs and fishes differs from that of the rest of amphibians, the birds, and the mammals, in that with the former group, gill filaments are formed early and are soon covered up, in frogs they gradually disappear, while in fish they are permanent, and these embryos soon swim freely about in the water.”
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