Public Release:  Researchers reveal types of genes necessary for brain development

PLOS

Researchers from Harvard Medical School and Brandeis University have successfully completed a full-genome RNAi screen in neurons, showing what types of genes are necessary for brain development. Details of the screen and its novel methodology are published July 4th in the open-access journal PLoS Genetics.

Recent advances in genomics, such as the sequencing of entire genomes and the discovery of RNA-interference as a means of testing the effects of gene loss, have opened up the possibility to systematically analyze the function of all known and predicted genes in an organism. Until now, this type of functional genomics approach has not been applied to the study of very complex cells, such as the brain's neurons, on a full-genome scale.

Dr. Katharine Sepp and her fellow researchers took fresh neuronal cells extracted from embryos of the fruit fly genus Drosophila and screened them using RNA interference techniques. The team tested all genes, one by one in a rapid manner, for their potential role in neuronal development. The team then validated the method in mice.

A combination of live-cell imaging and quantitative analysis allowed Sepp et al to characterize neurons' morphological phenotypes in response to RNAi-mediated gene knockdown. The researchers focused on 104 evolutionary conserved genes that, when downregulated by RNAi, have morphological defects. The team developed algorithms to help streamline the analysis of the thousands of images created in the process.

The analysis revealed unexpected, essential roles in neurite outgrowth for genes representing a wide range of functional categories including signaling molecules, enzymes, channels, receptors, and cytoskeletal proteins. Results also determined that genes known to be involved in protein and vesicle trafficking show similar RNAi phenotypes.

The researchers believe that this study provides an effective method for future studies of a large variety of genes, including those with important functions in the nervous system.

###

PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://www.plosgenetics.org/doi/pgen.1000111

CITATION: Sepp KJ, Hong P, Lizarraga SB, Liu JS, Mejia LA, et al. (2008) Identification of Neural Outgrowth Genes using Genome-Wide RNAi. PLoS Genet 4(7): e1000111. doi:10.1371/journal.pgen.1000111

CONTACT:

Dr. Katharine Sepp
ksepp@genetics.med.harvard.edu

PLEASE MENTION THE OPEN-ACCESS JOURNAL PLoS GENETICS (www.plosgenetics.org) AS THE SOURCE FOR THIS ARTICLE AND PROVIDE A LINK TO THE FREELY AVAILABLE TEXT. THANK YOU.

PLoS Genetics is an open-access, peer-reviewed journal published weekly by the Public Library of Science (PLoS).

Disclaimer

This press release refers to an upcoming article in PLoS Genetics. The release is provided by journal staff. Any opinions expressed in this release or article are the personal views of the journal staff and/or article contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the releases and articles and your use of such information.

About PLoS Genetics

PLoS Genetics (http://www.plosgenetics.org) reflects the full breadth and interdisciplinary nature of genetics and genomics research by publishing outstanding original contributions in all areas of biology. All works published in PLoS Genetics are open access. Everything is immediately and freely available online throughout the world subject only to the condition that the original authorship and source are properly attributed. Copyright is retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.

About the Public Library of Science

The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.