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 A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

nachricht CWRU researchers find a chemical solution to shrink digital data storage
22.06.2017 | Case Western Reserve University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

A new technique isolates neuronal activity during memory consolidation

22.06.2017 | Life Sciences

Plant inspiration could lead to flexible electronics

22.06.2017 | Materials Sciences

A rhodium-based catalyst for making organosilicon using less precious metal

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>