Summary: A recent Nature Neuroscience study reports it is glial cells, and not neurons, that direct the initial steps of brain assembly.
Source: Rockefeller University.
As the very first neurons come together to form the brain, they need pointers to end up in the right places. Where do these directions come from?
Rockefeller scientists have discovered that they originate from an unlikely source, revealing that the cells directing the very first steps of brain assembly are not other neurons, as scientists have long assumed, but so-called glial cells.
“While glial cells are abundant in the brain, their functions are much less understood,” says Shai Shaham, Richard E. Salomon Family Professor. “We’ve shown that in the roundworm C. elegans, glial cells play a pivotal role, coaxing neurons onto a specific path so that proper brain assembly can ensue.”
Shaham and his team also found that these worm glial cells are remarkably similar to their vertebrate counterparts.
To peek inside the earliest stages of brain development, scientists must observe and analyze embryos, which are notoriously tricky to study. But research associate Georgia Rapti, the lead author of a recent Nature Neuroscience report describing this work, was able to use C. elegans as a model to tease apart how brain assembly begins.
“We found that glial cells grow radial processes, or extensions, marking where the first axons must go, and they release multiple signals to guide neurons onto the correct path,” says Rapti. “Our experiments show that when glial cells or their signals are compromised, the worm’s brain is severely disrupted—more than 60 percent of its neuronal extensions fail to enter the brain as they normally would.”
Rapti and Shaham were also able to show that once glial cells have set the stage for brain assembly, a special group of 10 neurons, called pioneer neurons, are the first to follow suit. Pioneer neurons had previously been documented in other species, but their identities, molecular functions, and growth properties were generally unknown.
The researchers discovered a molecular signature for pioneer neurons, and showed that these cells can act with glial cells to recruit follower neurons. They were also able to uncover previously hidden molecular pathways that glial cells and pioneer neurons use to attract the next set of neurons into the brain.
While C. elegans may not seem to have a lot in common with humans and other vertebrates, their brain assembly processes resemble ours at the molecular level. For example, Rapti and Shaham note recent reports revealing that the assembly of the mouse spinal cord relies on a signaling molecule called Netrin, which is produced by radial glial cells. The researchers found that Netrin functions similarly in the worm—glial cells produce this molecule, which guides pioneer neurons to form the C. elegans brain.
“The glial cells driving brain assembly in the worm look like—and function similarly to—those in the vertebrate spinal cord,” says Shaham. “We think of glial cells as the Pied Piper for nervous system assembly across animals, and the Piper’s pipe appears to be the same from worms to mammals.”
Source: Katherine Fenz – Rockefeller University
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to Gaetz et al./Annals of Clinical and Translational Neurology
Original Research: Abstract for “Glia initiate brain assembly through noncanonical Chimaerin–Furin axon guidance in C. elegans” by Georgia Rapti, Chang Li, Alan Shan, Yun Lu & Shai Shaham in Nature Neuroscience. Published online August 28 2017 doi:10.1038/nn.4630
Glia initiate brain assembly through noncanonical Chimaerin–Furin axon guidance in C. elegans
Brain assembly is hypothesized to begin when pioneer axons extend over non-neuronal cells, forming tracts guiding follower axons. Yet pioneer-neuron identities, their guidance substrates, and their interactions are not well understood. Here, using time-lapse embryonic imaging, genetics, protein-interaction, and functional studies, we uncover the early events of C. elegans brain assembly. We demonstrate that C. elegans glia are key for assembly initiation, guiding pioneer and follower axons using distinct signals. Pioneer sublateral neurons, with unique growth properties, anatomy, and innervation, cooperate with glia to mediate follower-axon guidance. We further identify a Chimaerin (CHIN-1)– Furin (KPC-1) double-mutant that severely disrupts assembly. CHIN-1 and KPC-1 function noncanonically, in glia and pioneer neurons, for guidance-cue trafficking. We exploit this bottleneck to define roles for glial Netrin and Semaphorin in pioneer- and follower-axon guidance, respectively, and for glial and pioneer-neuron Flamingo (CELSR) in follower-axon navigation. Taken together, our studies reveal previously undescribed glial roles in pioneer-axon guidance, suggesting conserved principles of brain assembly.
“Glia initiate brain assembly through noncanonical Chimaerin–Furin axon guidance in C. elegans” by Georgia Rapti, Chang Li, Alan Shan, Yun Lu & Shai Shaham in Nature Neuroscience. Published online August 28 2017 doi:10.1038/nn.4630