Part 1: GENES' GUIDE TO EMBRYO DEVELOPMENT

One of the greatest mysteries of life seems to surround those signals that tell a developing embryo what it is to become. Even today, after endless observation we are still baffled by the subtle differences between developing embryos and their striking similarities during the early phases of growth. For instance, what makes a chick embryo become a chicken? And what forces guide a frog egg into becoming a living frog. It is the subtle signals that distinguish frog from chicken and that confuse and bewilder us as we observe embryos develop into adults.

One of the greatest mysteries of life seems to surround those signals that tell a developing embryo what it is to become. Mankind has marveled at the development of eggs and embryos from the beginning of recorded history. Even today, after endless observation we are still baffled by the subtle differences between developing embryos and their striking similarities during the early phases of growth. For instance, what makes a chick embryo become a chicken? And what forces guide a frog egg into becoming a living frog. We are all familiar with the striking similarities between frog embryos and chicken embryos at their very early stages of development. It is the subtle signals that distinguish frog from chicken and that confuse and bewilder us as we observe embryos develop into adults.

Molecular engineers have recently begun to unravel some of this mystery. By studying the sequencing of genes and the subsequent production of their proteins within developing embryos, scientists are able to determine at what point in that development are certain proteins produced.

One of the questions that has been raised by scientists over the years, has been how are certain genes "turned on" at certain times during development, while other genes seem to remain sleeping. In the developing chick a gene for the production of bone matrix seems to be activated at just the right moment as we imagine bone should start to form. If this gene is not activated the chick will develop as one of its phylogenic predecessors, an amphibian. Such a change is obviously disastrous to a developing chick, and is lethal. However, if instead of a chick the embryo were destined to be an amphibian, the absence of bone matrix, at that time, would be normal.

The interplay of many genes, literally twinkling on and off during the embryonic development, direct the orchestra of cells that make up the final adult form. Within this article we will review a few such genes and their subsequent influence on the embryonic development. We will develop a hypothetical embryo and watch its development from a single cell through several stages on its way to adulthood. Those genes that will be mentioned will be examples taken from several species for this demonstration. So the animal we will describe will not exist and indeed be a chimera. (A chimera is an animal that contains genes from other animals. Its name derives from the ancient mythological chimeras, such as the sphinx, griffin, centaur, satyr, etc.)

As a simplified example of how genes may be sequenced to produce proteins one after the other or at some appropriate stage of development, let's consider three genes: A, B and C. For this example gene A will be expressed first. Followed by the expression of gene B. Then gene C will produce its proteins. We will try to construct a mechanism that will give us some idea of how these three basically equivalent genes can be set to express their individual proteins in sequence rather than all at one time. Before we begin we might want to consider why this is important. If gene A produced red blood cells and gene B produced a heart and gene C produced muscle; we can imagine a sequence that would make sense for developing embryo. Obviously, you must have muscle before you can produce a muscular heart. If blood is to circulate and be pumped by the heart the embryo must develop a heart before it is able to pump blood. But there may be situations where blood develops before the heart. Or likewise the heart muscle could develop before the blood components. Some sequences are obvious. You must have eyes before you can see. You must have bones before you can stand. You must have muscles before you can move. Some sequences are not so obvious. Should you develop red blood cells before you develop fluid plasma? Or is one digestive enzyme a prerequisite to another? By studying the development of many embryos and the sequencing of many genes, scientists are beginning to uncover the mysteries of embryonic development.

Since genes are essentially chemicals, we have to wonder at their ability to 'turn on' or to 'turn off' at specific times or in specific sequences. Often we hear the misguided argument that they must 'know' when to activate and when to remain silent. In truth we can envision several very simple mechanisms that will permit genes to activate in sequence.

Genes direct the production of proteins. Let's picture the production of proteins by genes as taking place inside of separate rooms in a large building. Each gene manufactures a specific protein within a specific room. The proteins remain within these rooms until the doors are opened. Each room has a different lock which requires a specific key to open that door. For the sake of this discussion, the keys are enzymes. Each door will open under the influence of its matching enzyme.

Gene-A produces enzyme-A which opens the door to room-A. Enzyme-A now flows through the halls of our building (the body). Not only does this enzyme do what it does for the body but it also is the key for the room containing gene-B. As the concentration of enzyme-A builds up, the door to room-B slowly opens releasing enzyme or protein-B into the halls. Oddly, enough enzyme-B may actually force the door to room-A shut, thus turning off the production of any more enzyme-A. Or enzyme-B may have absolutely no effect on the production of enzyme-A. The key to door-C may be a combination of enzyme-A and enzyme-B. Once these enzymes have reached a level capable of opening the biochemical door to room-C, the gene-C may then begin to express its protein.

Such simple constructs explain how genes may be 'timed' for appropriate action within the developing organism. In this simple example we see that protein-A must appear first to release protein-B followed by the release of protein-C. In this model gene-C would never be expressed before gene-A or gene-B.

We should also consider the fact that different types of protein (and their differing functions) are produced by different genes. Some proteins may be enzymes. As explained in the above example, these are used to breakdown other substances. Some proteins may be globular forms. The hemoglobin in our blood is a good example of a globular protein. These bulky molecules are usually found within an organism carrying various other substances. Some proteins may function as hormones or regulators of the body's machinery. As their concentration changes, the function of certain organs also changes. All the many gene produces combine in sequence to construct a developing embryo. Each seems to have an assigned or preferred role in this construction. Each seems to have an optimal time for action. The interplay of these many genes and their associated proteins, all following the instructions set within the DNA, produce a living organism.