Study Provides New Insights Into Genes Involved In Mammal's Brain Development

Scientists at Penn State claim that they have for the first time used high-throughput sequencing to uncover active genes in developing brains.

The researchers believe that their work provides what is likely the best evidence thus far for the activity in the brain of such a large number of genes.

They say that the significance of their study lies in the fact that it provides new insights into the genes that are involved in a mammal's early brain development, including those that contribute to neurological disorders.

They hope that their findings may one day lead to the development of drugs or gene therapies that treat neurological disorders, such as autism and mental retardation.

Led by Distinguished Professor of Biology Hong Ma and Associate Professor of Biology Gong Chen, the research team used a high-throughput technique to sequence millions of messenger-RNA molecules, which carry genetic information from DNA molecules to protein molecules.

The researchers obtained the RNA from the brains of mice, which are an important model system for studying human biology.

They found that over 16,000 genes-more than half of the mouse's entire set of known genes, are involved in the brain's development and functions.

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"The brain represents one of the most, if not the most, complex organs in a mammal's body. So we weren't surprised to find that the number of genes that are active in the brain is so high," said Ma.

The researchers focused on two critical times during the development of a mouse's brain: embryonic day 18 (E18) and post-natal day 7 (P7).

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"These two time points represent major milestones during brain formation. Brain development in an 18-day-old embryo involves a significant amount of brain cells, or neurons. In contrast, brain development in a seven-day-old infant involves the formation of numerous connections between these neurons. Our goal was to determine which genes are active during these two critical times," said Ma.

The scientists examined genes that correspond to the RNA molecules from the cortex of a mouse.

"The cortex is the surface portion of the large brain that is responsible for most cognitive and sensory abilities," said Ma.

According to the researchers, more than 3,700 of the 16,000 genes identified by them have different levels of activity between the E18 and P7 time points.

"This differential activity tells us about the differences in the brain at these two stages. For example, the genes that are active at E18, but not at P7, probably are important during E18. We get some support for this notion when we see that certain genes that already are known to be involved in cell division are actively expressed during E18, while other genes that are known to play a role in building the connections between neurons are much more active at P7," said Ma.

What makes their findings even more interesting is the fact that some of the genes identified in mice are known to be matched to the human genes that are involved in neurological disorders, such as Alzheimer's disease, autism, and some forms of mental retardation.

"Our results can help to pinpoint the specific time during brain development when the genes related to certain diseases are active. This knowledge may help other scientists to develop drugs or gene therapies that can treat the diseases. For example, if a particular gene defect causes poorly constructed connections between certain neurons, a drug might be developed that enhances those connections to compensate for the gene defect," said Ma.

Ma has revealed that his future studies will look at some of the genes to see whether they are important for the brain to be formed properly.

The researchers also plan to study how genes function in development disorders of the brain.

A research article on their study has been published in the online edition of the Proceedings of the National Academy of Sciences.

Source-ANI
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