P&S Journal: Fall 1994, Vol.14, No.3
The Mystery of Embryo Development
How does a single fertilized egg cell develop into a complete frog, chick, human, or any other animal? Each creature inherits half its chromosomes from the father and half from the mother, and every cell in the mature animal's body will contain that full complement of chromosomes. How do the cells of the earliest stages of embryo life know how to orient themselves to make a head or a tail and all the other diverse tissues that are part of any developing animal and to put them in the right location?
This is a mystery that has puzzled geneticists since the inception of that science and is the field of research Dr. Claudio Stern has been pursuing for the past 20 years. Dr. Stern arrived at P&S Jan. 1, 1994, to become chairman of the Department of Genetics and Development. He spent the preceding 10 years at Oxford University, investigating embryonic genes to find out what signals pass between these early developmental cells that enables them to diversify.
A century ago, two experiments demonstrated that some signal does exist. A German researchist, Wilhelm Roux, took a frog egg immediately after its initial division into two cells and killed one cell with a hot needle, leaving its remnant attached to the remaining cell. The viable cell went on to develop into only half an embryo. A few years later the experiment was modified by Driesch and Spemann, who completely separated half of a two-cell embryo from the other. These two halves became two complete embryos. In fact, up to the embryo stage called the gastrula (which occurs at six to seven days in a human and eight to 10 hours in a chick) the chick embryo may be divided up like a pie, and each separate piece will become a complete embryo. In Roux's experiment the assumption is that some signal passed from the membrane of the killed cell into the viable cell to prevent the embryo from developing completely: Perhaps the viable cell "thought" the other half was still there to do its job because the cell membrane was still attached.
Any complete separation of an embryo before gastrulation results in identical twins, triplets, etc. However, at a later stage, incomplete separation occurs, producing Siamese twins, which also may be a result of complete separation and subsequent partial fusion. In that case, the degree to which the internal organs are shared depends on how far apart the two parts are and how soon they rejoin.
To determine what kinds of signals pass between embryonic cells and how these signals are mediated, Dr. Stern works with chick embryos in the gastrula stage, when the embryo resembles a flat disc with a groove down the middle called the primitive streak. It is from this streak that much of the embryo is derived; the surrounding outside cells become the placenta and the amniotic sac that holds the fetus.
At the tip of the primitive streak is a portion called Hensen's node. In the 1930s it was shown that this tip, transplanted into any part of another gastrula stage embryo, goes on to become a complete embryo. However, the only portions of the embryo derived from the graft are the internal organs. All of the new embryo's nervous system and epidermis are derived from the surrounding cells of the host embryo-cells that normally are fated to be placenta, amnion, or skin. These findings indicate that the transplanted portion of the primitive streak must produce something that changes the nature of the surrounding host cells so that not only do they go on to become a complete nervous system including a brain, but everything ends up in the correct location in the developing embryo. In other words, all the genes for nervous system development become correctly expressed in the host cells.
Dr. Stern determined that if Hensen's node is transplanted later in development (after the critical first eight to 10 hours) the transplant loses the ability to make a complete nervous system, with progressive head to tail loss of the forebrain, midbrain, and hindbrain. It appears that the genes responsible for this development are programmed to turn off or on sequentially after a certain stage.
A gene called "goosecoid" has been identified in a very early stage of embryonic development called the blastula stage, when the embryo resembles a flat disc with a group of cells called Koller's sickle (KS) concentrated at one side. KS cells express the gene goosecoid, which enables them to make neighboring cells also express that gene. These cells eventually become part of the primitive streak; depending upon a cascade reaction starting in the blastula stage and continuing into the gastrula stage, any primitive streak cell has the potential to become any body part. Those farthest from the tip become skin and those closest become internal organs and Hensen's node.
Cells expressing the goosecoid gene are called "organizer cells." They produce a substance that instructs some neighboring cells to turn on the goosecoid gene and others to become nervous tissue cells that do not express goosecoid.
To ascertain how the goosecoid gene works, Dr. Stern used a virus as a vehicle to introduce the gene into random non-goosecoid-expressing cells of an early chick embryo. He wanted to determine if another nervous system could be programmed. So far, he has not been able to introduce the gene early enough in development to get the desired effect. He discovered, to his surprise, that if the goosecoid gene is introduced into cells of the dorsal part of the brain, the cells become ventral brain. The signal to produce the dorsal brain, which occurs earlier in development, is counteracted by the later change in the implanted goosecoid gene.
Thus the gene may have two distinct functions: Early in development, it defines the "organizer," which determines where the nervous system will form. Later it tells some brain cells where they should be (dorsal or ventral). It also has been shown that genes not only change their signals as development progresses, but some eventually turn off completely while others may continue to be used for different purposes in adult life.