A gene that helps create diversity in the brain

In a very basic sense, the brain is composed of 2 kinds of cells: neurons and glia. Neurons are the brain cells that you usually see or think about when you open a science textbook. Glia, on the other hand, are so named because they were originally thought to be the “glue” of the brain; they held things together— supported. Now, we know that glia serve a much more important and dynamic function and they can even improve the function of neurons. Actually, there is a nice article on glia posted this week on the scienceblog.com main page.

Anyway, back to the cell types of the brain: neurons and glia. It gets more complicated, as it usually does when studying the nervous system. It turns out even if we just look at all the neurons in the brain,  there exists a huge variety of neuron types. The properties of these neurons depend on where they originate, where they end up, how many branches they have, their shape, and the chemicals they secrete.

But how is this variety established?

In the most recent issue of Nature Neuroscience, a research team out of Boston, MA (including researchers at both Harvard and MIT), has identified a gene that selects for neurons termed corticospinal neurons—neurons that participate in communicating information from the brain to the spinal cord. Just one of the many flavors of neurons that exist in our heads. In this study, the researchers demonstrate that the gene of interest, Fezf2, controls a subset of genes responsible for the identity of corticospinal neurons. Additionally, Fezf2 induces the expression of a neurotransmitter transporter, the glutamate vesicular transporter, responsible for packaging this chemical into the little packages of neurotransmitter that the neuron eventually spits out when it talks to other neurons. At the same time, Fezf2 also acts in a manner that suppresses the expression of a different transporter, this way the corticospinal neuron can only mainly secrete one type of chemical, a feature vital to its proper function.

What about the bit on connectivity that I promised? Well, Lodato et al. also found that Fezf2 can induce many genes related to the guidance of neuronal processes termed axons, the long extension that is responsible for carrying the action potential and secreting neurotransmitter. A neuron such as the corticospinal neuron must travel a long way to communicate to its appropriate target (from brain to spinal cord). It must also accurately navigate other brain structures and travel within the correct bundle of fibers. Many different proteins and chemical signals are responsible for this process. You can think of it like a dog following a scent. Chemical gradients and proteins help guide the axon by attracting or repelling it, ultimately steering the axon to the appropriate target. In this paper, the authors demonstrate that Fezf2 is required for the expression of one of these guidance proteins, ephb1, making it an important regulator of axon guidance.

Neurons are incredibly diverse and their development and connectivity is super complex. For these reasons, it is no wonder that so many genes and proteins are involved in making sure that the brain develops appropriately. On this note, it is also no wonder that there are so many neurological disorders. So many things must go right in order for the brain to work correctly—so many tiny little things. It leaves a lot of room for things to go wrong. Like any process in life that requires many moving parts (ie, your car, a project at work)…lose one, depending on what it is, you might get by. Lose another, it could be a long day.



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