[JFOCLIFFNOTES31102013] CHAPTER 3: YOUR INNER FISH
Posted on Sunday, November 3, 2013 at 10:50 PM

CHAPTER III: 

1.Introduction
  • Our body is made up of hundreds of different kinds of cells. This cellular diversity gives our tissues and organs their distinct shapes and functions. The cells that make our bones, nerves, guts and so son look and behave entirely differently. Despite these differences, there is a deep similarity among every cell inside our bodies: all of them contain exactly the same DNA. 
  • The pieces of DNA that turn on in every cell are called genes. A skin cell is different from a neuron because different genes are active in each cell. 
  • When a gene is turned on, it makes a protein that can affect what the cell looks like and how it behaves.
  • These genetic switches help assemble us. We start as a single cell that contains all the DNA needed to build our body. The plan for that entire body unfolds via the instructions contained in this single microscopic cell. Our bodies are a composition of individual genes turning on and off inside each cell during our development.
2. Making Hands
  • All 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.
  • In the 1950s and 1960s, Edgar Zwilling and John Saunders discovered that two little patches of tissue essentially controlled 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.
  • Another experiment, initially done by Mary Gasseling in John Saunders' laboratory, led to a powerful new line of research. If you took 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, the organism (in this case a chicken) will have a fully developed wing, except with a full duplicate set of digits. More remarkably, the new fingers were mirror images of the normal set.
  • Some molecule or gene inside that patch of tissue was able to direct the development of the pattern of the fingers. 
  • This finger duplication method can also be done by injecting Vitamin A at the right concentration and right stage.
  • This patch of tissue was named the zone of polarizing activity (ZPA). The ZPA is a patch of tissue that causes the pinky side to be different from the thumb side (in human finger terminology, where the human pinky is the fifth digit in animals).
  • People believed that the cells in the ZPA made a molecule that then spread across the limb to instruct cells to make different fingers. The key proposal was that it was the concentration of this unnamed molecule that was the important factor.
  • In areas close to the ZPA, where there is a high concentration of this molecule, cells would respond by making a pinky. In the opposite side of the developing hand, farther from the ZPA so that the molecule was more diffused, the cells would respond by making a thumb. Cells in the middle would each respond according to the concentration of this molecule to make a second, third and fourth fnger.
  • This concentration dependent idea was tested and proved by Denis Summerbell in 1979.

3. The DNA Recipe
Sonic the Hedgehod
  • The gene that made one end of a fly look different from another (similar to the ZPA concept) was nicknamed the hedgehog because the flies with the mutation in the gene had bristles that reminded them of a little Hedgehog. Key figures: Cliff Tabin (from Harvard), Andy MacMahon and Phil Ingham. Note that they were working on independent research before collaborating together.
  • Tabin, MacMahon and Ingham named the chicken version of the hedgehog a Sonic hedgehog after the Sega video game. 
  • Every limbed animal has the Sonic hedgehog gene, which is active in the ZPA tissue. If the Sonic hedgehog gene hadn't turned on properly during the eighth week of your own development, then you would either have a extra fingers, or your pinky and thumb would look alike. Occasionally, things go wrong with the Sonic hedgehog and your hand would end up looking like a broad paddle with as many as twelve fingers that look alike.
  • The DNA recipe to build upper arms, forearms, wrists, and digits is virtually identical in every creature that has limbs.
4. Giving Sharks A Hand
  • Sharks and their relatives are the earliest creatures that have fins with a skeleton inside.
  • One effect of the Sonic hedgehog is to make the fingers distinct from one another. As we saw with respect to the ZPA, what kind of digits develops depends on how close the digit is to the source of the Sonic hedgehog. 
5. Concluding Ideas
  • All appendages, whether they are fins or limbs, are built by similar kinds of genes.
  • The transition of fish fins into limbs did not involve the origin of new DNA: much of the shift likely involved using ancient genes, such as those involved in shark fin development, in new ways to make limbs with fingers and toes.
  • The connection within living creatures are deep: Tabin used flies to find a gene in chickens to tell us about human birth defects.

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