Duke University scientists have caught the very first glimpse of molecules shuttling along a sort of highway working the length of neural stem cells, which are crucial to the development of brand new neurons.
This new view offers given them an intriguing clue that a protein lacking in Fragile X syndrome, an autism-related disorder that triggers intellectual disability, is responsible for moving at least some of this molecular cargo up and down the stem cells. The findings show up online Dec. 1 in Current The field of biology .
“The moving molecules we noticed in these stem cells could be crucial for their function — including their decision to become neurons, ” said the particular study’s senior investigator Debra Silver, an assistant teacher of molecular genetics and microbiology at the Duke College School of Medicine. “We’re excited about these new breakthroughs and have many more questions. ”
Neural come cells are buried deep within the brain and task long, thin extensions outward. The ends of these cellular material, called “endfeet, ” go so far as to reach the top layer of the brain and prevent neurons, which climb upward these thin strands, from migrating further.
Compared to the cell’s main body, these far-flung endfeet reside in a vastly different environment of the brain. Their environment may influence whether a neural stem cell creates another stem cell or becomes a neuron. That dedication affects how many neurons the brain can generate.
These cells are so long that researchers thought that, such as neurons, they would need to ship some of their contents long ranges, including the messenger RNA molecule that is needed to manufacture protein.
After toiling with the microscope, postdoctoral specialist Louis-Jan Pilaz was, for the first time, able to see mRNAs relocating down the neural stem cell’s shaft, frame-by-frame.
“The [fluorescently tagged mRNAs] were stopping sometimes, and they would keep going, like they have an intention, ” Pilaz said. “No one had seen molecules moving only at that speed within neural stem cells before. ”
The results suggest that neural stem cells are roads for molecular transport, carrying not just mRNAs but also a number of other types of proteins, Silver said.
When mRNA reaches the endfeet it gets translated into proteins by other cellular machinery. Silver’s group was able to display this definitively with a new test they developed that permitted them to isolate the endfeet from the rest of the cell. Making use of fluorescent tagging, graduate student Ashley Lennox was able to imagine new proteins being made within the endfeet.
“[Until now], there have been really limited tools for being capable to evaluate this in an intact tissue, and that’s where the study provides a new model, ” Silver said.
Silver’s team knew that mRNA was delivered in a controlled fashion to the endfeet, rather than merely calming, but they didn’t know which other molecules might manage these steps. They examined a handful of molecules known to influence RNA dynamics and were surpised to find that the Fragile By syndrome protein called FMRP bound and carried the particular mRNAs.
Previous studies from several groupings have implicated FMRP in neural stem cell functionality, but very little was understood about its role within brain development.
The group found 115 various mRNAs that FMRP latched onto: about 30 percent of such are linked to brain diseases, and about half of those are usually enriched in autism. They picked one of these mRNAs plus showed, using a mouse model of Fragile X, that mRNA needed FMRP to arrive at the neural stem cell’s endfeet.
“This was really exciting. We clearly noticed enrichment of a subset of RNAs, that we were able to just validate using other methods, ” Silver said.
The group is conducting further studies to understand exactly how production of protein is controlled within the endfeet, plus whether it changes over the course of development. The scientists will also be working to parse FMRP’s different functions to gauge their particular effects on brain development.
Materials provided by Duke University . Unique written by Kelly Rae Chi. Note: Content material may be edited for style and length.