Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Generating genetic diversity in the nervous system

01.08.2002


Scientists from Baylor College of Medicine (Texas, USA) and the Wellcome Trust Sanger Institute (Cambridge, UK) have deciphered how neurons can synthesize a diverse range of proteins from a relatively limited number of genes – a discovery with important implications for understanding how complex neural circuitry is formed and maintained throughout our lives.



A long-standing question in neurobiology is how each of the tens of thousands of neurons that populate the mammalian brain are instructed to establish the specific connections that give rise to our complex neural networks. Researchers postulate that the expression of distinct sets of proteins in each individual neuron act as molecular cues to direct the course of each neuron’s fate. The protocadherin (Pcdh) family of proteins are prime candidates for this job, as each individual neuron expresses an overlapping but distinct combination of Pcdh proteins.

In the August 1 issue of Genes & Development, Dr. Allan Bradley and colleagues report on their identification of the mechanism of neuron-specific Pcdh expression. The Pcdh family of proteins is encoded by three gene clusters (Pcdh-a, Pcdh-ß, and Pcdh-g) on human chromosome #5, and mouse chromosome #18. The a and g clusters each contain genes with several variable exons (coding regions of DNA). Each variable exon can be separately joined to a constant region of the gene, thereby creating the genetic blueprint for a Pcdh protein that will have a unique variable region and a common constant region.


Dr. Bradley and colleagues have discovered that that although the Pcdh gene clusters share a similar genomic structure to the immunoglobin genes in the immune system -- where antibody protein diversity confers antigen-binding specificity -- the neuron-specific expression of Pcdh proteins is accomplished by an entirely different mechanism.

As Dr. Bradley explains, "We tested the various models by creating mice with a variety of modified alleles. The most intriguing theory was recombination (like the immunoglobulin genes), but we found no evidence to support this! Rather it appears that diversity is predominately generated using alternative promoters and cis-alternative splicing with a low level of trans-splicing."

The researchers found that each variable exon is under the regulatory control of its own promoter (a DNA sequence where RNA polymerase binds to initiate transcription of the gene into pre-mRNA). Once transcribed, the pre-mRNA transcript then predominantly undergoes an intramolecular reaction, known as "cis-splicing," whereby a variable exon is cut out and joined, or "spliced," to the constant region of that same pre-mRNA transcript. Ultimately, this process enables a neuron to manipulate the Pcdh gene structure to generate a number of mRNAs, each containing different variable regions, which will each be translated into a unique Pcdh protein.

This work establishes that through the use of multiple promoters and cis-splicing, individual neurons are able to express distinct combinations of Pcdh genes, and, in turn, proteins. Further work will delineate how the differential expression of Pcdh proteins may underlie the specificity of neural connectivity.

Heather Cosel | EurekAlert!
Further information:
http://www.cshl.org/

More articles from Life Sciences:

nachricht Cells migrate collectively by intermittent bursts of activity
30.09.2016 | Aalto University

nachricht The structure of the BinAB toxin revealed: one small step for Man, a major problem for mosquitoes!
30.09.2016 | CNRS (Délégation Paris Michel-Ange)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

Heavy construction machinery is the focus of Oak Ridge National Laboratory’s latest advance in additive manufacturing research. With industry partners and university students, ORNL researchers are designing and producing the world’s first 3D printed excavator, a prototype that will leverage large-scale AM technologies and explore the feasibility of printing with metal alloys.

Increasing the size and speed of metal-based 3D printing techniques, using low-cost alloys like steel and aluminum, could create new industrial applications...

Im Focus: New welding process joins dissimilar sheets better

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...

Im Focus: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Paper – Panacea Green Infrastructure?

30.09.2016 | Event News

HLF: From an experiment to an establishment

29.09.2016 | Event News

European Health Forum Gastein 2016 kicks off today

28.09.2016 | Event News

 
Latest News

First-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

30.09.2016 | Materials Sciences

New Technique for Finding Weakness in Earth’s Crust

30.09.2016 | Earth Sciences

Cells migrate collectively by intermittent bursts of activity

30.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>