Life through death

If it wasn’t for our cells’ ability to commit suicide, a process technically known as apoptosis, we would all be born with webbed fingers and toes. A bit like ducks and otters.

Sure, we would be better swimmers, but we wouldn’t be able to hold a pen, climb a tree or play the piano. And assembling an Ikea bookshelf would become even more of a nightmare than it already is. Can you imagine that?

Webbed-fingers, also known as syndactyly, is the most common congenital malformation of the human hand. It affects one in 2000 babies and it is often found to run in families. The “webbing” consists of a thin membrane, pretty much like normal skin, connecting the digits. It can be between two fingers only, more commonly between the long and the ring fingers, or it can run across the whole hand. This condition is caused by the cells in between the digits failing to undergo apoptosis when they should.

Syndactyly of the human hand (Flatt, 1994)

Syndactyly of the human hand (Flatt, 1994)

What do I mean? Well, we all have webbed-fingers during the first few weeks after conception and this is absolutely normal during early embryonic development. When everything goes to plan, after about 8 weeks the cells of the skin membrane connecting the digits start to die and disappear, resulting in the separation of fingers. Sixteen weeks after conception the process is complete and the unborn child is already the happy owner of ten perfectly separated fingers and toes. However, if this fails to happen and the cells making up the membrane between digits don’t commit suicide at the right time, the child is born with partial or full syndactyly.

The process by which healthy cells are sacrificed during development is known as morphogenesis by apoptosis. It means that groups of cells are able to induce their own death in the right place and at the right time to shape different organs of our body. You could think of this process as an artist carving a sculpture from a block of marble: first he starts from a rough outline, then he chisels and refines it until he’s left with the desired shape.

This is a very common event, not just in humans, but in pretty much all multicellular living things, from lower vertebrates to complex mammals. Since this process takes place so early in life and is crucial for the development and survival of the organism, it makes sense for it to be tightly regulated by the DNA. The first studies on the genetics of morphogenesis by apoptosis were conducted on the flatworm C.Elegans. This tiny creature starts with roughly 1100 cells and loses 130 during morphogenesis, leaving it with around 950 cells in total. For such a small animal, that is a lot of cells to sacrifice during development! The research then moved to flies, where three apoptotic genes were soon discovered to be involved in this process. Geneticists, who always come up with the best names, called them reaper, grim, and hid. Similar genes have since been found in mice, rats and humans, and it is now accepted that morphogenesis by cell death is under genetic regulation in all the animal kingdom. The development of limbs, the differentiation of the components of the eye, the complex anatomy of the ear, the fine connections between neurons in the brain, all of this happens thanks to genetically regulated death of perfectly healthy cells.

A great number of genes controlling apoptosis have already been identified in humans. Two genes in particular are involved with the separation of fingers in the hand. They are responsible for the production of proteins BMP2 and BMP4, which are found in the regions of skin between fingers where the cell death occurs. Experiments have also shown that the expression of the BMP protein antagonist noggin causes a reduction in cell death, resulting in congenital syndactyly.

So next time you find yourself performing simple arithmetics counting your fingers, remember that if it wasn’t for your cells’ sacrifice, you would just have to learn to do the damn thing in your head!

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