Navigation Links
Johns Hopkins scientists reveal nerve cells' navigation system
Date:5/9/2011

Johns Hopkins scientists have discovered how two closely related proteins guide projections from nerve cells with exquisite accuracy, alternately attracting and repelling these axons as they navigate the most miniscule and frenetic niches of the nervous system to make remarkably precise connections.

The discovery, reported April 28 in the journal Neuron, reveals that proteins belonging to the "semaphorin" family of guidance cues are crucial for getting neuronal projections exactly where they need to be not only across long distances, but also in the short-range wiring of tiny areas fraught with complex circuitry, such as the central nervous system of the fruit fly.

Because signaling that affects the growth and steering of neuronal processes is critical for repairing and regenerating damaged or diseased nerve cells, this research suggests that a more refined understanding of how semaphorin proteins work could contribute to treatment strategies, according to Alex Kolodkin, Ph.D., a professor in the neuroscience department at Johns Hopkins and a Howard Hughes Medical Institute investigator.

Using embryonic flies, some native (normal) and others genetically altered to lack a member of the semaphorin gene family or the receptor that binds to the semaphorin and signals within the responding neuron, the team labeled particular classes of neurons and then observed them at high resolution using various microscopy strategies to compare their axon projections.

In the native developing flies, the team saw how certain related semaphorins, proteins that nerve cells secrete into the intracellular space, work through binding their plexin receptor. First, a semaphorin-plexin pair attracts a certain class of extending neurons in the embryonic fly central nervous system assemble a specific set of target projections. Then, a related semaphorin that binds to that same plexin receptor repels these same neurons so as to position them correctly with in the central nervous system. Finally, the attractive semaphorin/plexin interaction assures the establishment of precise connections between these central nervous system axons and sensory neurons that convey messages about the external environment by extending their axons into the CNS from the periphery and contacting the assembled CNS pathways. Flies lacking this semaphorin/plexin signaling showed defects in these connections, which the researchers were able to reverse when these cues and receptors were re-introduced into flies lacking them.

To investigate whether the absence of semaphorin in flies had behavioral consequences, the team collaborated with investigators at Janelia Farm laboratories of the Howard Hughes Medical Institute and used specialized computer software to follow the movements of hundreds of fly larvae crawling on a small dish. The plate was perched on a large speaker that vibrated with pulses of sound, letting the team compare the movements of normal larvae to mutants missing semaphorin.

The "tracking" software measures differences in normal foraging behavior (mostly crawling straight and occasionally making turns) when a sound is activated. The larvae with intact semaphorin/plexin responded to sound stimulation by stopping, contracting and turning their heads from side to side. The semaphorin mutants failed to respond to the same stimuli. The researchers repeated the experiment using mutant larvae missing the protein to which semaphorin binds its plexin receptorand these larvae also showed no reaction to sound-vibration.

"The fly larvae sensory neurons, located on the larval body wall, send axon projections that do not make contact with their appropriate targets in the central nervous system when semaphorin/plexin signaling is absent," Kolodkin says. "This tells us that semaphorin cues guide not only neuronal processes assembly in the central nervous system, but also incoming projections from sensory neurons to the CNS targets."

The Kolodkin lab's experiments in the invertebrate fruit fly central nervous system mirror related findings in the mouse reported Feb. 10, 2011 in Nature. Then, they showed that a different semaphorin cue is important for certain neurons to make precise connections within the developing inner plexiform layer of the retina, an elaborately laminated club-sandwich-like structure that must be precisely wired for accurate visual perception in mammals.

To demonstrate that semaphorins are necessary for neuronal projections from distinct classes of neurons to make their way to correct layers in this retinal "sandwich," the scientists examined the retinas of 3-, 7- and 10-day-old mice that were genetically modified to lack either a member of the semaphorin gene family or its appropriate plexin receptor. These mutants showed severe connectivity defects in one specific inner plexiform layer, revealing faulty neuronal targeting.

"In two distinct neural systems in flies and mammals, the same family of molecular guidance cues semaphorins and their receptors mediate targeting events that require exquisite short-range precision to generate complex neuronal connectivity," says Kolodkin who, as a postdoctoral fellow in the mid-1990s, first discovered the large family of semaphorin guidance cues working with the grasshopper nervous system.

"This work begins to tell us how, in a very small but highly ordered region of the nervous system, select target innervation and specific synaptic contacts between different classes of neurons can be established in the context of evolving circuit complexity" Kolodkin says.


'/>"/>

Contact: Maryalice Yakutchik
myakutc1@jhmi.edu
443-287-2251
Johns Hopkins Medical Institutions
Source:Eurekalert

Related biology news :

1. Texas researcher Arthur E. Johnson to give prestigious ASBMB-Lipmann Lectureship
2. Johns Hopkins team creates stem cells from schizophrenia patients
3. Johns Hopkins researchers capture jumping genes
4. Encyclopedia of Life names Dr. Rebecca Johnson a 2011 Rubenstein Fellow
5. Johns Hopkins researchers reshape basic understanding of cell division
6. UNCs Dr. Sean McLean receives Robert Wood Johnson Foundation award
7. American Society for Microbiology honors Ryan Johnson
8. Case Western Reserve University works with Johnson & Johnson Services Inc. on research grant
9. Pancreatic Cancer Action Network-AACR Pathway to Leadership Grant awarded to Johns Hopkins Early Career investigator
10. Johns Hopkins scientists discover a controller of brain circuitry
11. JDRF announces diabetes research program with Johnson & Johnson
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/28/2017)... , March 28, 2017 The ... Hardware (Camera, Monitors, Servers, Storage Devices), Software (Video Analytics, ... Region - Global Forecast to 2022", published by MarketsandMarkets, ... 2016 and is projected to reach USD 75.64 Billion ... and 2022. The base year considered for the study ...
(Date:3/24/2017)... 24, 2017 The Controller General of Immigration from ... Abdulla Algeen have received the prestigious international IAIR Award for the ... Continue Reading ... ... Controller Abdulla Algeen (small picture on the right) have received the IAIR ...
(Date:3/23/2017)... The report "Gesture Recognition and Touchless Sensing Market by Technology (Touch-based ... to 2022", published by MarketsandMarkets, the market is expected to be worth USD ... 2022. Continue Reading ... ... ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... and LAGUNA HILLS, Calif. , Oct. ... Cancer Research, London (ICR) and University ... SKY92, SkylineDx,s prognostic tool to risk-stratify patients with multiple myeloma ... MUK nine . The University of Leeds ... partly funded by Myeloma UK, and ICR will perform the ...
(Date:10/10/2017)... ... 2017 , ... San Diego-based team building and cooking events company, Lajollacooks4u, has ... The bold new look is part of a transformation to increase awareness, appeal to ... period. , It will also expand its service offering from its signature gourmet cooking ...
(Date:10/10/2017)... 10, 2017 International research firm Parks Associates announced ... at the TMA 2017 Annual Meeting , October 11 in ... residential home security market and how smart safety and security products impact ... Parks Associates: Smart Home ... "The residential security market has ...
(Date:10/9/2017)... DIEGO , Oct. 9, 2017  BioTech ... biological mechanism by which its ProCell stem cell ... critical limb ischemia.  The Company, demonstrated that treatment ... amount of limbs saved as compared to standard ... the molecule HGF resulted in reduction of therapeutic ...
Breaking Biology Technology: