Download What is Notch?

What is Notch?
Explanation provided by Christopher Hughes, PhD
Chairman, Cure HHT’s Global Research and Medical Advisory Board
Your body contains trillions of cells, and all of these developed from a single fertilized egg. How
did we get from one tiny cell to be large, complex people, made up of brain cells, heart cells,
liver cells and all the rest? One cell became two, and those two became four, and those four
became eight… and at each step the daughter cells had to decide what they would become.
Would they stay the same type as the parent cell? Would they each become heart cells? Would
one stay the same and one become a kidney cell?
Each time that cells have to make these kinds of decisions they turn on a gene called notch.
When this gene is in the “on” position a cell can get to choose what it will be, and that decision
will be based on how old the cell is, on signals from other cells, and on what the body’s needs
are. If notch is “off” then the daughter cell does not get to choose and will likely be the same as
its parent.
By the way, you may be wondering why the gene is called “notch”. About a hundred years ago
scientists started working on fruit flies as a model system to understand genetics. Nobody knew
what a gene was back then, but the scientists did know that certain traits could be inherited.
One of these traits was a “notch” in the fly’s wing. Half a century later that defect was found to
be caused by a defective gene, and that gene was named notch in honor of the phenotype (or
problem) it caused when it went wrong. You may be surprised, but notch is just one of many,
many genes that flies and humans share!
In later life notch still has a role in the proper functioning of the body - helping cells to make
choices (often called “cell fate decisions”). For example, notch has an important role in the
proper functioning of blood vessels and can help determine whether you make an artery (which
carries blood away from the heart) or a vein (which carries blood back to the heart).
There is now mounting evidence that problems with decisions regarding whether a vessel
should become an artery or vein may underlie the formation of arteriovenous malformations
(AVMs) - the vascular defects that are the key feature of HHT.