Some Basic Developmental Processes And Some Genes They

We have identified a few generic principles by which spatial and temporal differentiation takes place. We can now describe how these same principles are employed in a repertoire of basic developmental processes that characterize much of development in animals and even plants. The same sets of genes appear again and again in different developmental contexts, even in the same organism. Many or even most regulatory pathways have homologs in vertebrates as well as invertebrates, or even in animals and plants—the kind of deep conservation referred to in Chapter 3 and elsewhere. These are often used in logically similar developmental patterning across diverse species, and in fact this pathway homology has helped establish homologies between traits that had been thought for more than 150 years (since Darwin) only to be analogous, that is, similar in function but independently evolved. Indeed, deep conservation and multiple use of genetic mechanisms have seriously challenged the concepts of analogy and homology themselves.

Primary Axis Specification

An embryo quickly establishes structured asymmetry (polarity) along at least one and usually two or three anatomic axes. Subsequently, many new axes or asymmetries are established, often in a nested way. Position along a temporal or physical axis is correlated with the expression of different genes or gradients of the same genes. Primary axis specification is fundamental and, once laid down by evolution, has stubbornly retained many of its essential features.

We have described how concentration gradients establish aspects of axes of the fly embryo. Homologous genes are used in vertebrates in an interesting way that relates to long-standing questions about the evolutionary relationships between the two major groups of animals—and showing what was, when discovered, surprising evidence of our common ancestry. As shown in Figure 9-5, the relative DV positions of the central nerve axis and gut are oriented similarly relative to early expressed genes, even though these signals are "inverted" between vertebrates and invertebrates relative to the DV axis. Proteins coded by the homologs Chordin in vertebrates and Sog in invertebrates bind the homologous proteins from Bmp4 and Dpp, respectively, preventing the Bmp4/Dpp signal from being received by local cell surface receptors. Product encoded by the homologs Xolloid/Tolloid inactivates Chordin/Sog, allowing Bmp4/Dpp signal to be received by the receptors inducing neurogenic ectoderm. In a sense, the default cell fate of ectoderm is neural, so this antagonistic relationship prevents ectoderm in nonneural regions from becoming neural. Thus the Chordin/Sog genes "protect" a region from becoming neurogenic ectoderm. These are quantitative inductive interactions and have been shown experimentally to work across the vertebrate-invertebrate divide (e.g., vertebrate genes having their same effect in invertebrate embryos). Sometimes a conserved series of pathway interactions is found in both groups though performing different functions, but sometimes there is functional homology that reawakens notions of the unity of animal form that had gone out of acceptability a century or more ago.

It was hypothesized in the early 19th century by Geoffroy St Hilaire that invertebrates were "inverted" vertebrates (or vice versa). Figure 9-5A shows a forced example to position an invertebrate—a cuttlefish, and a vertebrate—a bird, suggested by two little-known authors, trying to show that the two types of animal were of essentially the same design; this figure was drawn by investigators who themselves had been drawn into a famous heated debate in 1830 between Geoffroy and his former colleague Georges Cuvier, about the extent to which the similarities were true (Appel 1987). Although there are clear similarities between vertebrates and at least some invertebrates (mouth and head at one end, anus and reproductive organs at the other, limbs branching out along the side, and so forth), at that time the homology of this overall organization, much less the skeletal, neural, digestive, and other systems was not clearly established. The uncertainty was probably made worse by the fact that this was before Darwin and hence before common ancestry was a serious explanation of body-plan similarity (Richards 1992).

Even after Darwin, and despite these overall differences, the known ancestral forms and fossils were such that it still seemed fanciful to suggest that a vertebrate was an inverted insect. However, the kind of genetic patterning data recounted above breathed surprising new life at least into the general idea. It seems clear that today's deuterostomes (chordates) and protostomes (worms, arthropods) have dorsoventrally inverted body plans relative to each other, both in terms of morphology and the expression of genes associated with corresponding structures (Figure 9-5B). In both groups, TGFfi genes (Bmp/Dpp) repress, but antagonists (Chordin/Sog) locally counteract that signal to permit, neural commitment. How this works in flies was described above; in vertebrates the combined action of the developmental signal b-catenin and Nodal-related proteins activates Chordin in the midline, repressing Bmp expression and allowing neural development (De Robertis et al. 2000; Gerhart 2000; Nielsen 1999).

Does this indicate that St Hilaire was right after all (Holley et al. 1995)? Clearly this seems to be so in the sense that the conserved but inverted anatomic relationships are matched by conserved but inverted gene induction patterns. However, an inversion would require one of the two forms to be ancestral, and rather than an inversion per se the common ancestor might have had a less dorsoventrally specific body plan, or have been intermediate in other ways between what we consider today to be two distinct body plans; the means of expression of these homologous genes in the two groups is different and some primitive animals have less distinct DV orientation than either vertebrates or arthropods (Gerhart 2000). Modifications over evolutionary time of the pattern of migration of cells that will take neural fate, relative to the locations of the mouth at the blastopore stage, could provide an explanation without requiring a real and more complicated inversion event (Fitch and Sudhaus 2002; van den Biggelaar et al. 2002).

Since the discovery of this conserved aspect of polarity, which made a wonderful story of the resuscitation of a prescient kind of guess that had been long ridiculed, many more kinds of homology have been observed between vertebrates and invertebrates. It is probably fair to say that major elements of most corresponding systems, and many if not most basic cell types, share at least some homologous gene expression. Table 9-1 provides a number of these, and Wilkins (Wilkins 2002) presents a thorough discussion of the prominent examples known to date. Of course, the concept of homology relative to specific structures is challenged by the fact that many of the shared genes, such as the Hox and many other TF and SF genes, have numerous sites of expression, making it likely that some similarities might occur even by chance, an implication of the powerful "strategy" of evolution to use and reuse a limited toolkit.

Darwin would be pleased, because this confirms his ideas about common ancestry, but with entirely new types of data. However, it is tempting to overstate the homologies. Geoffroy's idea of "inversion" included the exoskelton of invertebrates corresponding to the internal skeleton of vertebrates (e.g., a vertebra corresponding to the exoskeletal elements of an arthropod limb). We know that Hox and other genes like Bmps and Distalless TFs are used in both, but they really are not very similar. Even if homologous pathways are used in similar ways, they are embedded in different overall organizational contexts. Thus the fly wing and vertebrate fore-limb are both limbs, and their overall polarity is established by some strikingly

Figure 9-5. Comparison of stereotypical body plans for vertebrates and invertebrates to show the idea that they are inversions of the same overall plan. (A) Alleged similarity between vertebrate (bird) and invertebrate (cuttlefish) sent to St Hilaire in the 1830s by otherwise unknown authors Meyranx and Laurencet, and published by his opponent Georges Cuvier (Couvier 1830); (B) vertebrates and invertebrates have a common body plan in many ways, but with a 180 degree dorsoventral rotation.Top row is invertebrate, bottom vertebrate. Left are correspondingly oriented copies of an image of Geoffroy's inversion hypothesis by Wilder (Wilder 1909), right are transverse sections of the body plans of each animal type showing the major basic structures; to the right of that are genes involved in early dorsoven-tral patterning showing their conserved usage. For more homologies see Table 9-1, and see text.

AE&LEBBV1E

st VERTEBRATE pr

Fig. 140. Reversible diagram illustrating the Annelid theory. Reversible designations, applying to both forms; S, brain; X, nerve cord; H, alimentary canal. Designations applying to Annelid only; m, mouth; a, anus. Designation applying to Vertebrate only; st, stomatodeum; pr, proctodeum; nt, notochord.

ANNELID/ARTHROPOD dorsal

ventral dorsal

Chordin heart visceral mesoderm gut axial muscle nerve cord

Chordin ventral nerve cord axial muscle gut visceral mesoderm heart ventral

CHORDATE (VERTEBRATE)

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