A recent study sheds light on how a gene connected to the production of the new brain cells does its job.
The findings by a team of North Carolina State University researchers could pave the way to new therapies for brain injury or disease.
Dr. Troy Ghashghaei, assistant professor of neurobiology, had previously found a gene - known as Foxj1-connected to the production of an area inside the olfactory bulb where stem cells could form.
He and his team have now discovered that Foxj1 was an 'off switch' that told neuronal stem cells to stop reproducing and triggered the development of a stem cell "niche" in the olfactory bulbs.
However, further experiments with newly developed genetically modified mice unexpectedly revealed that a fraction of Foxj1-expressing cells actually functioned as stem cells. But they only did so until the mouse reached the age equivalent of a human toddler, not throughout adulthood. In addition, the number of neurons generated by these cells was much lower than expected, which led to more questions about its function.
"Essentially, the experiments we did weren't giving us the numbers of neurons from Foxj1-expressing stem cells that we expected. We could have gotten disappointed with what may have been perceived as a road-block in our findings" said Ghashghaei.
"If the gene was one that stem cells had to express in order to produce neurons, then we should have seen a greater number of neurons produced from the Foxj1-expressing stem cells. Instead, only about three percent of the olfactory neurons came from the Foxj1 stem cells. More importantly, we could not identify these unique neurons as belonging to known types of neurons in the olfactory system," added Ghashghaei.
These findings and subsequent experimentation helped the team discover that in addition to being an off switch, the Foxj1 cellular lineage (i.e., Foxj1 expressing cells and their descendents) performs an important function as a "conductor," instructing the other stem cells in the olfactory bulb by secreting various molecules that affect the other stem cells' behaviour and ensure their correct development into neurons. So a small number of Foxj1-expressing cells and their neuronal offspring direct other stem cells to continue reproducing, and may be telling them when to become functionally integrated neurons.
"This finding is important because for the most part our brains cannot generate new neurons, nor can we efficiently use transplanted neurons to repair damage," said Ghashghaei.
"Foxj1 expressing cells and their neurons seem to support zones within the brain where new neurons are created and integrated into existing neural circuits. If we can find out how to put these 'conductor' cells into other areas of the brain such as the spinal cord, it may lead to new cell-based therapies.
"This project took us on a roller-coaster ride - but the ending is a testament to the power of creative thinking and persistence in scientific inquiry - an achievement of which the clever and hardworking graduate students and postdoctoral fellows working on the problem should be very proud," added Ghashghaei.
The research is published in the Journal of Neuroscience.