Neural Versus Nonneural Development Dj Vu All Over Again

In Chapter 3, we discussed a proposed mechanism for the way in which sog functions to promote neural development in the neuroectoderm. The central premise of that hypothesis is that the diffusible Dpp protein produced in the nonneural ectoderm of the fly embryo leaks into the adjacent neural ectoderm where, in principle, it can activate its own expression though a positive feedback loop (see Figs. 3.9 and 3.10). In this scheme, Sog prevents the invasive combination of Dpp diffusion and autoactivation from spreading into the neuroectoderm thereby permitting cells to follow their preference to become neural. In support of this hypothesis, Dpp can invade the neuroectoderm of mutants lacking the sog gene and convert much of it into nonneural ecto-

Fly embryo

Frog embryo

D Spemann

D Inversion ^----^organizer

Neuroectoderm = default state

FIGURE 5.5. Equivalence of neural development in vertebrates and invertebrates.

D Spemann

D Inversion ^----^organizer

Neuroectoderm = default state

FIGURE 5.5. Equivalence of neural development in vertebrates and invertebrates.

derm. This conversion of neural ectoderm into nonneural ectoderm results from suppression of neural gene expression and from activtion of nonneural genes (e.g., dpp) in the neuroectoderm.

A remarkable indication of the preservation of D/V patterning during the evolution of vertebrates and invertebrates is that zebrafish mutants lacking the function of the chordin gene have defects nearly identical to those of sog mutants described above. In these mutants, expression of the bmp4 gene spreads from the nonneural ectoderm into the neural ectoderm, indicating that BMP4, like its fly counterpart Dpp, is capable of diffusing and autoactivating. As a consequence of the spread of BMP4 signaling into the neuroectoderm in chordin mutant fish embryos, the formation of neural structures is compromised and the region of the embryo giving rise to nonneural structures is enlarged. Thus, in both vertebrates and invertebrates, a key function of "neural inducers" is to protect the neuroectoderm from invasion by BMP4 or Dpp, respectively. In this way, Chordin and Sog permit ectodermal cells to follow their default preference to become neuroectoderm (Fig. 5.5).

As we discuss further in Chapter 6, the commonalities between developmental mechanisms in vertebrates and invertebrates provide a basis for reconstructing the form of the most recent common ancestor of vertebrates and invertebrates. From what we have discussed in this chapter, it is clear that this ancestor was a highly structured creature which was subdivided into segments along the A/P axis and partitioned into basic tissue types along the D/V axis. In the near future it should be possible to draw a fairly detailed image of this wondrous creature that gave rise to most animal forms alive on earth today.

■ Summary of Early Vertebrate Development ■

The mechanisms by which vertebrate mothers polarize their eggs seem to be quite different from those employed by flies. For example, in flies, the mother polarizes the A/P axis by creating a graded distribution of the Bicoid morphogen and the D/V axis by generating a graded distribution of the Dorsal morphogen. In frogs, on the other hand, the mother polarizes the egg into animal and vegetal hemispheres, and an external agent (the sperm) defines the opposing position of the dorsal organizing center. Also, patterning of the A/P and D/V axes is coupled in frogs, whereas these axes are established by entirely independent mechanisms in the fly embryo. Although not enough is known about early mechanisms involved in patterning the A/P and D/V axes of other vertebrates, it seems likely that diverse mechanisms initiate axis patterning in different vertebrate species.

Despite the differences in creating initial asymmetries in the egg, an abundance of evidence indicates that there are deep similarities in how embryos use maternally provided information to generate segments along the A/P axis and to partition the D/V into primary tissue types such as neural versus nonneural ectoderm. During mid-gastrulation at the so-called phylotypic stage, embryos from across the animal kingdom share obvious features of segmentation. During this "phylotypic" stage, homeotic and Hox genes label segments according to their position along the A/P axis in flies and vertebrates, respectively. These segment-identity genes organize segment-specific developmental programs in corresponding regions of the fly and vertebrate embryo. The most dramatic demonstration that vertebrate and invertebrate embryos employ a common de velopmental mechanism for assigning segment identity was provided by the McGinnis experiment in which it was shown that mouse Hox genes could mimic the function of their fly counterparts during fly development. This seminal observation laid the groundwork for subsequent studies that have revealed a more detailed web of common mechanisms guiding early developmental decisions in all segmented animals.

Common mechanisms are also shared between vertebrates and invertebrates in subdividing the embryo into primary tissue types along the D/V axis. In both classes of organisms, the default state of ectoderm is neural, and, in the nonneural ectoderm, this neural preference is actively suppressed by cells sending a mutually inhibitory signal to one another. The molecular identity of this inhibitory signal is the same in vertebrates and invertebrates (i.e., BMP4 in vertebrates = Dpp in flies). In flies the neural suppressive activity of Dpp is blocked in the neu-roectoderm by Sog. Similarly, Chordin, the vertebrate counterpart of Sog, blocks the neural suppressive activity of BMP4 and thereby functions indirectly to promote neural development. In both vertebrate and invertebrate embryos an important mechanism by which such neural-inducing substances act is to block a positive feedback loop created by the coupling of Dpp/BMP4 diffusion and autoactivation. As in the case of segment-identity genes along the A/P axis, these early-acting D/V patterning genes function when transplanted between vertebrates and invertebrates.

An important implication of the deep similarities in the primary patterning mechanisms driving vertebrate and invertebrate development is that the most recent common ancestor of all segmented animals must have been a highly evolved creature with well-defined segments and primary tissue types. This emerging image of our shared ancestor as a shrimp-like creature is several orders of magnitude more complex than the amoeboid slug-like organism that was the generally imagined form of this ancestor just 15 years ago. This realization is one of the most profound insights into evolution that one can extract from our current understanding of development.

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