What is it about?
Neurons receive information through their parts called dendrites, which are often organized in shapes that look like trees. Evidently, correct shape of these trees is very important for normal information processing. This shape is mostly defined during development by the action of genetic factors. However, it is little known what happens to the shape of the trees if the dose of each genetic factor is higher or lower than normal. In this article I systematically looked at the published studies on the shaping of dendritic trees during development in one specific sensory neuron in the common fruit fly. Surprisingly, I found that in 72% of cases trees are very sensitive to the dose of genetic factors, meaning that their shape will form incorrectly either the gene dose is higher or lower than it should be. In addition to that, each gene seems to have a specific response curve in regard on how it affects tree shape.
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Why is it important?
The conclusions brought forward in this article about how sensitive dendritic trees are to the exact gene dose available inside the neuron are important for three main reasons. First, response curves can be useful to understand how genetic factors work; for example two factors that follow the same curve type may be more likely to act in the same cellular process. Second, this knowledge can help researchers working on dendritic tree shaping to interpret better the results of genetic rescue experiments. This means that if we know that trees are so sensitive (in 74% of cases) to the precise gene dose, then we should not be surprised if we fail to rescue 100% the phenotypes we are studying; it is very hard by genetic tools we currently use in genetic rescue experiments to replicate the exact gene dose under which the tree will develop normal shape and size. The third reason is that this knowledge can be helpful in drug design; several neurodevelopmental disorders (one of them being the Rett syndrome) can be caused by either too low or too high dose of a single genetic factor, which seem to lead to problems in the shape and size of dendritic trees. Clearly, if we want to design successful drugs for such disorders in the future we will need to study carefully the exact gene dose that cases such problems.
Perspectives
When I was trying to understand why the gene whose role I was studying in dendritic tree development (protein kinase A - PKA) seemed to cause the same problems in tree development either I increased of decreased the quantity of its activity levels, I wanted to know whether this was a weird effect confined to this specific gene, or whether it was something that occurred more frequently with genes that regulate dendritic tree shape and size. Apparently, after looking systematically at the problems that 47 genes cause to one specific sensory neuron in the fruit fly, I found that this is in fact quite a common phenomenon. Trees seem to sense the levels of their genetic regulators with extreme precision and they are highly responsive to any abnormal changes in their levels. Dendritic trees form fine structures and do so obviously via very refined mechanisms of sensing genetic factors quantities.
Tijana Copf
Institute of Molecular Biology and Biotechnology (IMBB), Crete, Greece
Read the Original
This page is a summary of: Importance of gene dosage in controlling dendritic arbor formation during development, European Journal of Neuroscience, August 2015, Wiley,
DOI: 10.1111/ejn.13002.
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