5.2Formation of the Body Structure—Organogenesis

After the three germ layers are formed, each grows into the following organs: the ectoderm develops into the skin, sensory organs, and neural tissue, such as the brain and spinal cord; the mesoderm develops into muscle tissue and bones; and the endoderm develops into the digestive organs, lungs, and the liver. This process is called "organogenesis." The formation of the brain and spinal cord together with the formation of the central nervous system is an example of organogenesis.
The formation of the central nervous system is an important event in the course of animal development because the central nervous system includes some of the most important organs in vertebrates and their formation occurs during the first stage of development. In the first stage of the formation of the central nervous system, a part of the ectoderm invaginates and forms a tubular structure called a "neural tube." The brain is then formed by enlargement of the front of this neural tube, and the spinal cord is formed from the back of it (Fig. 5-2).

Fig. 5-2. Development of the Brain

This shows the development of the brain and spinal cord from the neural tube. The front portion of the neural tube elongates and forms the brain, and the spinal cord is formed from the remaining portion of the neural tube. A complete view of the neural tube in the embryo is shown in a mouse embryo.

Several common mechanisms operate during the formation of the neural tube and other physical structures. One such mechanism is interactions between germ layers. For example, the mesoderm and ectoderm interact when the neural tube is formed from the ectoderm. Such interactions are carried out through inducers secreted from each germ layer and through adhesion among the cells. Examples of the activity of these inducers can be demonstrated experimentally. For example, when the germ cells of frogs are activated by the secretory protein activin, a type of inducer, formation of various tissues and organs is induced in response to its concentration (Fig. 5-3). Activation from outside of cell (for example, by inducers) to form various kinds of cells is referred to as "cell differentiation" (see Section 3 of Chapter 5).
Understanding of the molecular mechanisms of cell differentiation and organogenesis during development is deemed important academically and contributes greatly to the development of regenerative medicine, as described below. Thus, recent developments in research of molecular developmental biology, including cloning technology (see Chapter 11), have a major effect on the society.
There is also another important mechanism that is common to the formation of all animal organs. It is the activity of a cluster of genes called "homeotic genes" (see Column at the bottom). These genes are essential because they are expressed in a specific pattern in the embryo during the course of animal development, and thus, determine what kind of tissue or organ each region of the embryo will become.

Fig. 5-3. Formation of Tissue and Organs by Activity of Inducers

A piece of tissue is removed from a frog blastula and cultured in a culture medium containing activin, an inducer. Formation of various tissues is induced depending on the concentration of activin.


Homeotic Genes

Column Fig. 5-1. The Expression Patterns and Roles of Homeotic Genes

A) Excessive formations in fruit flies caused by mutations. In mutant flies, wings are formed in the portions where halters (for balance during flight) are formed in normal flies. Similarly, in dragonflies and butterflies, four wings are formed instead of two.
B) The HOM-C gene of fruit flies and the Hox gene of vertebrates are formed by the same gene cluster. In the development of flies and vertebrates, the HOM-C and Hox gene clusters are expressed with the same patterns from the head to the tail of the embryo. The formation of the basic physical structure of a fruit fly is determined by the expression patterns of HOM-C. Similarly, the formation of the basic structure of the brain, spinal cord, and gastrointestinal tract in mammals is determined by the expression patterns of the Hox gene cluster. Homeotic genes thus perform an important role in the formation of basic structures of the bodies of animals. indicates the direction and positional relationship between gene groups expressed in the embryo.

Even in organisms with completely different phenotypes, such as insects and humans, the molecular mechanisms that form their bodies actually have many points in common. One of these is the role that genes called "homeotic genes" play in the course of development.
Studies using fruit flies (Drosophila) have revealed mutations that cause formation of physical structural abnormalities, such as the formation of legs in heads and the formation of four wings instead of two (Column Fig. 5-1A). Recent studies of mutations in molecular genetics research have shown that these mutations are caused by a cluster of genes called the "homeotic gene complex" (HOM-C).
Homeotic genes are expressed in fixed patterns in developing embryos to determine what kind of tissue or organ each region of the embryo will become. Therefore, mutations in these homeotic genes cause major morphological abnormalities in the physical structures of the flies, as described above.
Subsequent research has shown that a gene cluster similar to the HOM-C of fruit fly exists in many animals, including humans. In vertebrates, it has been discovered that there are four sets (HoxA-D) of a gene cluster called Hox that corresponds to HOM-C. The HOM-C and Hox gene clusters are similar not only in structure but also in many other ways, including in the expression patterns they exhibit during the course of development and the roles they play in forming the structures of the body (Column Fig. 5-1B). This fact indicates that homeotic genes are conserved during the process of evolution and that they play an important role in the molecular mechanisms common to the formation of all animal bodies.

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