Navigation Links
Salk scientists identify key nerve navigation pathway
Date:11/21/2007

LA JOLLA, CA Newly launched nerve cells in a growing embryo must chart their course to distant destinations, and many of the means they use to navigate have yet to surface. In a study published in the current issue of the journal Neuron, scientists at the Salk Institute for Biological Studies have recovered a key signal that guides motor neurons the nascent cells that extend from the spinal cord and must find their way down the length of limbs such as arms, wings and legs.

The Salk study, led by Samuel Pfaff, Ph.D, a professor in the Gene Expression Laboratory, identifies a mutation they christened Magellan, after the Portuguese mariner whose ship Victoria was first to circumnavigate the globe. The Magellan mutation occurs in a gene that normally pilots motor neurons on the correct course employing a newly discovered mechanism, their results demonstrate.

In the mutants, growing neurons can be seen leaving the spinal cord normally but then appear to lose direction. The elongating cells develop kinks and sometimes fold back on themselves or become entwined in a spiral, forming coils outside the spinal cord. They appear to become lost in a traffic roundabout, described Pfaff, who observed the growing neurons with fluorescent technology.

Understanding how motor neurons reach the appropriate targets is necessary for the implementation of novel therapies, including embryonic stem cell replacement for the treatment of presently incurable disorders such as Lou Gehrigs disease, in which motor neurons undergo irreversible decay.

Embryonic studies provide useful insights on how to replicate the system in an adult, said Pfaff. And, as he also pointed out, the mechanisms used by motor neurons are likely to be similar to those used in other parts of the central nervous system, such as the brain. The Magellan mutation discovered by Pfaffs group was found in mice, but the affected gene, called Phr1, has also been identified in other model systems, including fruit flies and the worm species C. elegans.

A growing nerve bears at its bow a structure called the growth cone, a region rich in the receptor molecules whose job is to receive cues from the environment, much as ancient mariners who observed the stars and set their course accordingly. During development, the growth cone continuously pushes forward, while the lengthening neuron behind it matures into the part of the cell called the axon. Once the growing cell lands at its target in a muscle cell, it is the axon that will relay the messages that allow an animal to control and move its limbs at will.

In Magellan mutants, Pfaffs team discovered that the growth cone becomes disordered. Rather than forming a distinct cap on the developing neuron, the cone is dispersed in pieces along both the forward end and the axon extending behind it.

The defect is found in the structure of the neuron itself, said Pfaff, noting that the fundamental pieces, such as the receptors capable of reading cues, all seem to be present. Without the correct orientation of receptors, however, signals cannot be read accurately, resulting in growth going off course.

A precise gradient normally exists across the cone, said Pfaff, which is disrupted in the Magellan mutants. As a result, cells lose their polarity. They literally do not know the front end from the back end, according to Pfaff. This sense of polarity is a universal feature common to all growing neurons. Therefore, Phr1 is likely to play a role in most growing neurons to ensure their structure is retained at the same time they are growing larger, he said.

Pfaff and his group identified Magellan using a novel system they had developed, in which individual motor neurons and axons can be visualized fluorescently. They were able to screen more than a quarter of a million mutations, and the mutations of interest were rapidly mapped to known genes as a result of the availability of the sequenced mouse genome a byproduct of the effort to sequence entire genomes such as that in the human.

The Magellan mutation is located in a gene known as Phr1, which is also active in other parts of the nervous system, indicating that it most likely functions to steer other types of neurons, such as those that enervate sensory organs or connect different regions of the brain. Studies of Magellan may therefore shed light on how a variety of neurological disorders might be treated with cell replacement strategies.


'/>"/>

Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-4100 x1340
Salk Institute  
Source:Eurekalert

Related biology news :

1. UK scientists working to help cut ID theft
2. Scientists show that mitochondrial DNA variants are linked to risk factors for type 2 diabetes
3. Comet probes reveal evidence of origin of life, scientists claim
4. Scientists link fragile X tremor/ataxia syndrome to binding protein in RNA
5. Male elephants get photo IDs from scientists
6. Scientists retrace evolution with first atomic structure of an ancient protein
7. Muscle mass: Scientists identify novel mode of transcriptional regulation during myogenesis
8. Carnegie Mellon scientists develop nanogels that enable controlled delivery of carbohydrate drugs
9. Clemson scientists shed light on molecules in living cells
10. Scientists tackle mystery mountain illness
11. T. rex quicker than Becks, say scientists
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Salk scientists identify key nerve navigation pathway
(Date:3/31/2016)... RATON, Florida , March 31, 2016 ... LEGX ) ("LegacyXChange" or the "Company") ... for potential users of its soon to be launched ... video ( https://www.youtube.com/channel/UCyTLBzmZogV1y2D6bDkBX5g ) will also provide ... the use of DNA technology to an industry that ...
(Date:3/23/2016)... 23, 2016 ... Gesichts- und Stimmerkennung mit Passwörtern     ... MESG ), ein führender Anbieter digitaler ... mit SpeechPro zusammenarbeitet, um erstmals dessen Biometrietechnologie ... die Möglichkeit angeboten, im Rahmen mobiler Apps ...
(Date:3/21/2016)... Massachusetts , March 22, 2016 ... facial recognition with passcodes for superior security   ... ), a leading provider of secure digital communications services, ... their biometric technology and offer enterprise customers, particularly those ... secure facial recognition and voice authentication within a mobile ...
Breaking Biology News(10 mins):
(Date:4/29/2016)... , April 29, 2016 ... by Transparency Market Research "Separation Systems for Commercial ... Growth, Trends, and Forecast 2015 - 2023", the ... at US$ 10,665.5 Mn in 2014 and is ... from 2015 to 2023 to reach US$ 19,227.8 ...
(Date:4/29/2016)... , ... April 29, 2016 , ... Intelligent Implant Systems ... the FDA via 510(k) for sale in the United States. These components expand ... thoraco-lumbar fusions. With one-level sales beginning in October of 2015, the company has ...
(Date:4/28/2016)... NEW YORK , April 28, 2016 /PRNewswire/ ... biotechnology acceleration company reports the Company,s CEO  was ... capital titled Accelerators Enter When VCs Fear To ... Life Science Leader magazine is an ... work for everything from emerging biotechs to Big ...
(Date:4/28/2016)... York, NY (PRWEB) , ... April 28, 2016 ... ... QuickSTAT has made significant investments in recruiting top industry experts, and expanding its ... Platform, which provides industry-leading tools for clients to manage their clinical trial projects. ...
Breaking Biology Technology: