Navigation Links
Following direction: How neurons can tell top from bottom and front from back
Date:6/19/2014

TORONTO The question of how neurons and their axons establish spatial polarity and direction in tissues and organs is a fundamental question of any organism or biological system. Our cells and axons precisely orient themselves in response to external cues, but what are the core pathways and how are they integrated?

Lead author Dr. Naomi Levy-Strumpf and principal investigator Dr. Joseph Culotti developed a novel conceptual framework, published on-line in PLoS GENETICS, June 5 2014.

They investigated netrin and Wnt, signaling pathways that are implicated in cancer as well as in normal development. Working with C. elegans, they found that the UNC-6/netrin guidance cue, which has a conserved role in guiding cell and growth-cone migrations along the dorso-ventral axis, contributes to establishing antero-posterior polarity. Meanwhile, Wnts that are critical for determining polarity and guidance along the A/P axis are also involved in setting up polarity along the D/V axis. This provides a novel conceptual view of how A/P and D/V guidance signals are integrated intracellularly to generate polarized migration.

Redundancy goes both ways

An unexpected finding is that each pathway is redundant in both in A/P and D/V guidance, and in diverse processes that are involved in viability. "This redundancy tends to mask the roles of netrin and Wnt signaling in various biological processes," says Dr. Levy-Strumpf. "Now that we have identified the redundancy we can get a better insight into the concerted contribution of these two key signalling pathways in normal development as well as in tumor progression and metastasis." She is a research associate in the Culotti lab. Dr. Culotti is a Senior Investigator at the Lunenfeld-Tanenbaum and is a Professor of Molecular Genetics at University of Toronto.

'By means of a comprehensive genetic analysis, we found that simultaneous loss of Wnt and netrin signaling components reveals previously unknown and unexpected redundant roles for Wnt and netrin signaling pathways in both D/V and A/P guidance of migrating cells and axons in C. elegans, as well as in processes essential for organ function and viability. Thus, in addition to providing polarity information for migration along the axis of their gradation, Wnts and netrin are each able to guide migrations orthogonal to the axis of their gradation.'

"These results suggest the existence of novel mechanisms for guiding cell migrations that are different from previously demonstrated mechanisms involving simple attraction toward or repulsion away from a guidance cue. Now we're trying to illuminate them," says Dr. Culotti.

"This is an excellent example of the power of genetic analysis of the worm in neurobiology," says Dr. Jim Woodgett, Director of the Lunenfeld-Tanenbaum. "The exquisite sensitivity of being able to track the migration behavior of a single neuron coupled with robust tests is simply not possible yet in mammalian models. Yet now that this pathway interaction has been shown to occur, it'll only be a matter of time for someone to replicate it in mice."

The paper, "Netrins and Wnts Function Redundantly to Regulate Antero-Posterior and Dorso-Ventral Guidance in C. elegans," was published online in PLoS GENETICs on June 5, 2014. Funders include the Canadian Institutes for Health Research, Canadian Foundation for Innovation, Canada Research Chairs, and Mount Sinai Hospital Foundation.


'/>"/>
Contact: Polly Thompson
pthompson@lunenfeld.ca
41-658-648-002-046
Lunenfeld-Tanenbaum Research Institute
Source:Eurekalert

Related medicine news :

1. Antibody therapy prevents gastrointestinal damage following radiation exposure in mice
2. Risk of suicide and fatal heart attack immediately following a cancer diagnosis
3. Men and women receive different fertility advice following cancer diagnosis
4. U.S. Mammography Rates Drop Following Task Force Recommendations
5. Following the genomic pathways to stop the spread of cancer
6. Complications following 2-level axial lumbar interbody fusion
7. Surgical patient safety program lowers SSIs by one-third following colorectal operations
8. Anti-clotting therapy may be used too often following orthopaedic surgery or trauma
9. Increase in respiratory symptoms following volcanic eruption
10. Study uncovers simple way of predicting severe pain following breast cancer surgery
11. Survival excellent following living donor liver transplantation for acute liver failure
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... June 25, 2016 , ... First Choice Emergency Room , the ... Ogunleye, as the Medical Director of its new Mesquite-Samuell Farm facility. , “We ... new Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical Director of First Choice ...
(Date:6/25/2016)... ... , ... On Friday, June 10, Van Mitchell, Secretary of the Maryland Department ... in recognition of their exemplary accomplishments in worksite health promotion. , The Wellness at ... Wellness Symposium at the BWI Marriott in Linthicum Heights. iHire was one of 42 ...
(Date:6/24/2016)... ... , ... Those who have experienced traumatic events may suffer from a complex ... as drug or alcohol abuse, as a coping mechanism. To avoid this pain and ... a traumatic event. , Trauma sufferers tend to feel a range of emotions, from ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Pulmonary Hypertension ... that it will receive two significant new grants to support its work to ... its 25th anniversary by recognizing patients, medical professionals and scientists for their work ...
(Date:6/24/2016)... ... June 24, 2016 , ... Comfort Keepers® of San Diego, CA is ... Road To Recovery® program to drive cancer patients to and from their cancer treatments. ... the highest quality of life and ongoing independence. Getting to and from medical ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... Mass. , June 24, 2016   Pulmatrix, ... pharmaceutical company developing innovative inhaled drugs, announced today that ... Russell Investments reconstituted its comprehensive set of ... "This is an important milestone for Pulmatrix," ... will increase shareholder awareness of our progress in developing ...
(Date:6/24/2016)... 24, 2016  Arkis BioSciences, a leading innovator ... more durable cerebrospinal fluid treatments, today announced it ... funding is led by Innova Memphis, followed by ... private investors.  Arkis, new financing will accelerate the ... market release of its in-licensed Endexo® technology. ...
(Date:6/23/2016)... June 23, 2016 Research and Markets ... Market - Forecast to 2022" report to their offering. ... method for the patients with kidney failure, it replaces the ... from the patient,s blood and thus the treatment helps to ... chloride in balance. Increasing number of ESRD ...
Breaking Medicine Technology: