Scientists at St. Jude Children's Research Hospital have given investigators around the world free access to a powerful tool for studying brain development.
The Internet-based tool, called the mouse Brain Gene Expression Map (BGEM), is one of the largest gene expression maps of an organ ever developed, according to the St. Jude researchers. They say the map will likely help scientists discover the genetic origins of brain cancers, which could speed development of novel drugs to treat them.
The continual updating and completion of the BGEM Web site will be crucial to scientists. More than half of the approximately 25,000 genes in the mouse are thought to be involved in the development and function of the nervous system, but scientists have determined the function of only 30 percent of them. Many brain disorders, such as tumors and some psychiatric diseases, are also believed to be caused by gene mutations that arise during development of this complex organ.
A report on the development and availability of the BGEM appears in the March 28 issue of PLoS Biology. The Web site is http://www.stjudebgem.org/
The similarity of the mouse and human brain make this map useful to researchers who study the development of the human brain and the origin of brain tumors from gene mutations, according to Tom Curran, Ph.D., co-chair of Developmental Neurobiology at St. Jude. "The BGEM represents a new strategy for exchanging information among researchers that will accelerate our understanding of the human nervous system," he said. "I foresee a time when researchers will be able to do certain studies to confirm hypotheses using a computer interface that links our data to many other kinds of gene information, without the need to go into a regular laboratory."
The BGEM is a growing, encyclopedic collection of tens of thousands of images as seen through a microscope. The images are obtained at distinct time points and show where and when specific genes are expressed at each of four developmental stages. Gene expression is visible because special tags called probes bind to messenger RNA (mRNA) -- the decoded form of the gene -- and release a signal that can be seen using a special microscope. Gene expression refers to the production of mRNA, which becomes the blueprint the cell uses to make the protein coded for by that gene.
The BGEM links these images with the most up-to-date information on those genes, such as their function, location on chromosomes and exact DNA sequence. The BGEM gathers this information through direct links to the scientific databases PubMed, LocusLink, Unigene and the Gene Ontology Consortium, which is housed at the National Center for Biotechnology Information in the National Library of Medicine. In turn, the BGEM images are used by the Gene Expression Nervous System Atlas (GENSAT), which seeks to document the expression of all genes in the nervous system. GENSAT is supported by the National Institute of Neurological Diseases and Stroke (NINDS), and a partnership of 14 institutes and centers of the National Institutes of Health (NIH), which have formed a consortium to accelerate breakthroughs in understanding the nervous system. St. Jude undertook the BGEM project under subcontract from Rockefeller University (New York) on behalf of NINDS.
"A researcher who discovers a previously unrecognized gene that is expressed during brain development can rapidly determine how it fits into the overall scheme of brain development," said Craig Brumwell, PhD, the GENSAT manager in St. Jude Developmental Neurobiology. "The BGEM helps researchers skip over much of the drudgery of digging up information from the literature or from other databases."
The BGEM already contains detailed information and images of the expression of hundreds of genes that play key roles directing brain development, controlling the expression of other genes, guiding protein production and transporting molecules within the cell.