In The Growth Process Of Neurons, Most Important Actors Identified

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In The Growth Process Of Neurons, Most Important Actors Identified

(Moderator's note: This has the potential to help arrest CMT)

http://www.medicalnewstoday.com/medicalnews.php?newsid=53971

Defects in the growth process of our neurons often underlie brain or

nerve diseases, such as Alzheimer's disease or multiple sclerosis.

Scientists from the Flanders Interuniversity Institute for

Biotechnology (VIB) connected to the Katholieke Universiteit Leuven,

led by Bassem Hassan, have achieved a major step in unraveling the

growth process of axons, the offshoots of neurons. They have

identified the JNK, Wnt and FGF signaling cascades as the most

important actors and have also discovered their respective roles.

Their research shows that the growth of axons and the activity of

neurons are completely independent of each other. This new finding

can lead to better understanding of a variety of nerve diseases.

A complex network A human being has approximately 100 billion

neurons, the body's information and signal processors. The great

majority of them are found in the central nervous system. The brain

contains complex networks of neurons that regulate a large number of

bodily functions. Because the brain and the nervous system are a

delicate system, something can sometimes go seriously wrong and a

brain or nerve disease appears - for example, Alzheimer's or

Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), or

Multiple Sclerosis (MS). In the quest for possible cures for these

diseases, it is important that we understand how connections are

established between neurons.

Neurons have a number of long thin offshoots - called axons - that

conduct electrical impulses. These primary elements of information

transfer in the nervous system can sometimes be more than a meter

long. The axon's orientation as it grows is also of great importance

in forming the right connection. As in-coming stimuli are converted

into signals that determine the direction and speed of an axon's

growth, three things can happen: the axon can grow further, pull

back, or change direction. Therefore, axon growth is a process that

consists of several components: growth of the axon, orientation,

recognition of objectives, and finally formation of synapses in

order to transmit stimuli. Unraveling precisely how this whole

process works is important for understanding the development of the

brain and for helping develop therapies for diseases that are the

consequence of damaged or diseased neurons.

The fruit fly as model Bassem Hassan is using the fruit fly

(Drosophila melanogaster) as model for his research. Many processes

in this small fly are in fact comparable to processes in humans,

even for something as complex as the nervous system. Axon growth is

a complicated process in that it involves growth as well as

orientation and recognition. So it's not surprising that many

different genes are involved. To bring clarity to this complex

organization, Mohammed Srahna and his colleagues, led by Bassem

Hassan, have been studying the DCN (Dorsal Cluster Neurons), a group

of cells in the fruit fly's brain. The DCN belong to the visual

system of the adult fruit fly and stimulate the visual cortex. The

axons of the DCN form a very stereotypical connection pattern. This

well-ordered pattern gave the researchers the perfect starting point

for studying the influence of various genes on the axon growth

process.

Regulation by several genes From their study of the developing brain

of an adult fruit fly, the researchers have found that axon growth

is mediated by an interaction among three signal cascades: Wnt, FGF

and JNK. JNK is necessary for stimulating the growth of axons. Wnt

activates JNK and FGF inactivates JNK, so the right balance between

Wnt and FGF provides for a precise regulation of the growth of

neurons. Axonal growth turns out to be completely independent of

neuronal activity. This finding brings greater clarity to the axon's

growth process - knowledge that constitutes a major step forward in

understanding neuronal disorders.