Your Inner Fish: A Journey Into the 3.5-Billion-Year History of the Human Body by Neil Shubin Read Free Book Online Page B

Grail of our developmental research is to understand what genes differentiate the various bones of our limb, and what controls development in these three dimensions. What DNA actually makes a pinky different from a thumb? What makes our fingers distinct from our arm bones? If we can understand the genes that control such patterns, we will be privy to the recipe that builds us.
    All the genetic switches that make fingers, arm bones, and toes do their thing during the third to eighth week after conception. Limbs begin their development as tiny buds that extend from our embryonic bodies. The buds grow over two weeks, until the tip forms a little paddle. Inside this paddle are millions of cells which will ultimately give rise to the skeleton, nerves, and muscles that we’ll have for the rest of our lives.
     

The development of a limb, in this case a chicken wing. All of the key stages in the development of a wing skeleton happen inside the egg.
     
    To study how this pattern emerges, we need to look at embryos and sometimes interfere with their development to assess what happens when things go wrong. Moreover, we need to look at mutants and at their internal structures and genes, often by making whole mutant populations through careful breeding. Obviously, we cannot study humans in these ways. The challenge for the pioneers in this field was to find the animals that could be useful windows into our own development. The first experimental embryologists interested in limbs in the 1930s and 1940s faced several problems. They needed an organism in which the limbs were accessible for observation and experiment. The embryo had to be relatively large, so that they could perform surgical procedures on it. Importantly, the embryo had to grow in a protected place, in a container that sheltered it from jostling and other environmental disturbances. Also, and critically, the embryos had to be abundant and available year-round. The obvious solution to this scientific need is at your local grocery store: chicken eggs.
    In the 1950s and 1960s a number of biologists, including Edgar Zwilling and John Saunders, did extraordinarily creative experiments on chicken eggs to understand how the pattern of the skeleton forms. This was an era of slice and dice. Embryos were cut up and various tissues moved about to see what effect this had on development. The approach involved very careful microsurgery, manipulating patches of tissue no more than a millimeter thick. In that way, by moving tissues about in the developing limb, Saunders and Zwilling uncovered some of the key mechanisms that build limbs as different as bird wings, whale flippers, and human hands.
    They discovered that two little patches of tissue essentially control the development of the pattern of bones inside limbs. A strip of tissue at the extreme end of the limb bud is essential for all limb development. Remove it, and development stops. Remove it early, and we are left with only an upper arm, or a piece of an arm. Remove it slightly later, and we end up with an upper arm and a forearm. Remove it even later, and the arm is almost complete, except that the digits are short and deformed.
    Another experiment, initially done by Mary Gasseling in John Saunders’s laboratory, led to a powerful new line of research. Take a little patch of tissue from what will become the pinky side of a limb bud, early in development, and transplant it on the opposite side, just under where the first finger will form. Let the chick develop and form a wing. The result surprised nearly everybody. The wing developed normally except that it also had a full duplicate set of digits. Even more remarkable was the pattern of the digits: the new fingers were mirror images of the normal set. Obviously, something inside that patch of tissue, some molecule or gene, was able to direct the development of the pattern of the fingers. This result spawned a blizzard of new experiments, and we learned that this effect can be