Ever since school we all remember easily recognizable shape of neurons. They have distinctive branching shapes. Those branches are dendritic arbors – for more than a hundred years it is known that they differ in size and shape depending on neuron type. However, only now scientists at the RIKEN Brain Science Institute in Japan have found a factor, which helps shape dendritic arbors. It turns out that the protein centrosomin prevents dendrites from branching out.
There are structural elements, called microtubules, which push the ends of dendrites out in specific directions. These microtubules grow from one end and are often likened to cellular scaffolding. Scientists were interested how microtubule growth and dendritic branching is regulated, which is why they used Drosophila fruit flies in their experiments to determine how neurons get their branching shapes. The research team focused on sensory neuron of the fruit fly that has very limited dendritic branching and expresses the transcription factor called Abrupt.
By examining this sensory neuron from the fruit fly scientists quickly understood that expression of Abrupt has direct correlation with size of dendritic arbors – stronger expression of Abrupt leads to reduced arbors, while its absence leads to more complex arbors. Then the researchers examined the pathway of molecular events initiated by Abrupt, looking for a protein, which regulates microtubules.
Scientists narrowed search down to centrosomin. It is a protein that makes microtubule-based structures which are necessary for cell division. Team of scientists then found that loss of centrosomin creates more extensive dendritic branching, while stronger expression or addition of it can block the increase in branching caused by lack of Abrupt. Afterwards researchers discovered that in combination with another protein called pericentrin centrosomin can control where new microtubules form within the dendrites.
Microtubule does not push out new dendritic branches as it grows, when it is attached to something. But when it is not attatched to anything and forms at no particular site, new branches are more likely to form as it grows. Furthermore, while continuing their research, scientists found why centrosomin is so important. It turns out that centrosomin acts as glue that fixes microtubules. It mostly fixes them to Golgi bodies, which is why presence of centrosomin promotes less complex branching.
Scientists note that in case of neurological diseases the shape and complexity of neuronal dendrite arbors are often disrupted. Adrian Moore, leader of the research team, said: “it turns out the two microtubule regulators we found in this study of Drosophila neurons—centrosomin and pericentrin—are encoded by genes mutated in some human brain disorders. As we learn more about how neurons control the growth of dendrites it will help us understand these diseases more completely, and we may learn how to initiate and direct neuron growth as therapy for diseases and after neuronal injury.”
In other words, this discovery may help develop knowledge about how neurons form as they grow. This, in turn, may provide background for novel therapies where growth of neurons can be stimulated using special compounds. Potentially, it could help a lot of people suffering from neuronal injury, because such injuries take a lot of time and efforts and rarely heal completely. However, this is only a first step towards that direction and we can only hope that other steps will be as successful.