As the brain develops, neuronal axons extend outward in search of other neurons, all the while receiving ‘directions’ from the extracellular environment in the form of chemical signals that indicate when and where these growing axons should turn.
For example, axons exposed to a gradient distribution of nerve growth factor (NGF) protein will automatically steer in the direction of highest NGF concentration.
“NGF is one of the most extensively studied molecules that direct axon elongation,” explains Hiroyuki Kamiguchi of the RIKEN Brain Science Institute in Wako. “However, it has remained unclear for a long time how axons change the direction of elongation in response to NGF.”
NGF-mediated turning is facilitated in part by the cellular signaling molecule inositol trisphosphate (IP3), which in turn governs the intracellular release of calcium ions—an essential component of NGF’s chemo-attractive action. By applying advanced methods for molecular-resolution live cell imaging, Kamiguchi and his colleagues have now gained valuable insights into how this process directs axonal guidance1.
The researchers cultured chick-derived neurons expressing a genetically encoded sensor that fluoresces at specific wavelengths in the presence of IP3, and then observed how individual neurons responded to an NGF gradient in the vicinity of the growth cone—the leading edge of a growing axon. They immediately noted the establishment of an asymmetric distribution of IP3 within the growth cone and an elevated signal on the growth cone side exposed to higher NGF levels; this is mirrored by a similarly uneven distribution of IP3-induced calcium release. This asymmetry correlates directly with axonal turning such that the growth cone steers in the direction established by the highest levels of NGF, IP3 and calcium ion (Ca2+) release.
The development of techniques for accurately detecting potentially subtle variations in IP3 distribution was a key component of their success in this work. “We needed to detect 1% differences in fluorescence emission from the IP3 sensor between both sides of the growth cone,” says Kamiguchi.
However, he considers even the mere existence of such a gradient across the 10–20 micron width of the growth cone to be fairly surprising. “Because IP3 diffuses so rapidly in cytoplasm, it has not been viewed as a highly localized messenger,” he says. “This suggests the existence of robust degradation machinery to localize IP3 signals to one side of the growth cone.”
These insights into how neurons establish direction-specific signaling profiles should provide helpful starting points for understanding other models of cell polarization and migration.
The corresponding author for this highlight is based at the Laboratory for Neuronal Growth Mechanisms, RIKEN Brain Science Institute.
Saeko Okada | Research asia research news
Further reports about: > Brain > IP3 receptors > NGF > NGF concentration > RIKEN > Science TV > asymmetric distribution > axonal guidance1 > cellular signaling molecules > chemo-attractive action > molecular-resolution live cell imaging > neurons > spatial distribution of cellular signaling molecules
'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology
Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University
Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
23.10.2017 | Event News
17.10.2017 | Event News
10.10.2017 | Event News
23.10.2017 | Life Sciences
23.10.2017 | Physics and Astronomy
23.10.2017 | Health and Medicine