The Questions of Developmental Biology

The cilia cause the flow of fluid in the yolk sac cavity from right to left. When Nonaka
and colleagues (1998) knocked out a mouse gene encoding the ciliary motor protein dynein (see
Chapter 7), the nodal cilia did not move, and the situs (lateral position) of each asymmetrical
organ was randomized. This finding correlated extremely well with other data. First, it had long
been known that humans having a dynein deficiency had immotile cilia and a random chance of
having their hearts on the left or right side of the body (Afzelius 1976). Second, when the gene
for the iv mutant mice described above was cloned, it was found to encode the ciliary dynein
protein (Supp et al. 1997).
In some way (perhaps through the product of the inv gene), this leftward motion of the
cilia activates the genes for two paracrine factors, Nodal and Lefty-2, in the lateral plate
mesoderm on the left side of the embryo (Figure 11.44A). The proteins produced by these factors
spread throughout the left side of the embryo, and appear to be restrained to that side by the
Lefty-1 protein, which is secreted by the bottom left side of the neural tube (Meno et al. 1998).
Lefty-2 appears to be able to block the Snail protein (which becomes specific for the right side of
the body), while Nodal activates pitx2 gene expression (Pedra et al. 1998).
The development of mammals has enormous importance for understanding the bases of
numerous human diseases. In the next chapters, we will discuss later aspects of vertebrate
development and the relationship between genetics and development during organ formation.
Snapshot Summary: The Early Development of Vertebrates
1. Fishes, reptiles, and birds undergo discoidal meroblastic cleavage, wherein the early cell
divisions do not cut through the yolk of the egg. These cells form a blastoderm.
2. In fishes, the deep cells form between the yolk syncytial layer and the enveloping layer. These
cells migrate over the top of the yolk, forming the hypoblast and epiblast layers. On the future
dorsal side, these layers intercalate to form the embryonic shield, a structure homologous to the
amphibian organizer. Transplantation of the embryonic shield into the ventral side of another
embryo will cause the formation of a second embryonic axis.
3. There appear to be two signaling centers supplying anterior-posterior information in fishes, one
located at the border between the neural and surface ectoderm, the other in the lateral mesoderm.
4. In chick embryos, early cleavage forms an area opaca and an area pellucida. The region
between them is the marginal zone. Gastrulation begins at the posterior marginal zone, as the
hypoblast and primitive streak both start there.
5. The primitive streak is derived from anterior epiblast cells and the central cells of the posterior
marginal zone. As the primitive streak extends rostrally, Hensen's node is formed. Cells migrating
through Hensen's node become chordamesoderm (notochord) cells. These extend up to the
presumptive midbrain, where they meet the prechordal plate.
6. The prechordal plate induces the formation of the forebrain; the chordamesoderm induces the
formation of the midbrain, hindbrain, and spinal cord. The first cells migrating laterally through
the primitive streak become endoderm, displacing the hypoblast. The mesoderm cells then
migrate through. Meanwhile, the surface ectoderm undergoes epiboly around the entire yolk.