HSCI scientists identify gene involved in the language regions of the brain
By Jessica Lau
Scientists at Boston Children’s Hospital (BCH) and the Harvard Stem Cell Institute (HSCI) have discovered a gene involved in brain development, specifically in the areas related to speech and language.
Their study, led by first author Richard Smith, Ph.D., is published in Neuron. The co-senior authors are Maria Lehtinen, Ph.D., associate professor of pathology at BCH and HSCI Affiliate Faculty member, and Christopher Walsh, M.D., Ph.D., Chief of the Division of Genetics at BCH and HSCI Principal Faculty member.
The researchers first focused on a family affected by polymicrogyria — a condition where the folds on the brain’s surface are smaller and more numerous than usual — in the brain region responsible for language. By analyzing the family’s genomes, the researchers identified a mutation in the gene SCN3A.
Expanding their search, the researchers identified several other families with polymicrogyria and SCN3A mutations. Many of the affected individuals had difficulties with speaking and moving the facial muscles involved in speech.
To figure out how SCN3A plays a role in speech, the researchers delved into the gene’s mechanism. SCN3A makes a protein that sits in the cell membrane and controls how much sodium passes in and out. When measuring individual cells containing the mutated protein, the researchers found that the sodium levels were altered. Other data showed that SCN3A was active during fetal brain development, not after birth.
Finally, the researchers tested the mutated SCN3A in an animal model. The brains showed abnormal structure, with disrupted folding patterns and neurons that did not move to the correct layers.
These findings open new avenues of investigation for understanding speech development in the fetal brain.
“This study helps us to better understand not just neurodevelopmental disorders, but also the development of the central nervous system more generally,” said Paola Arlotta, who co-leads the HSCI Nervous System Diseases Program along with Clifford J. Woolf, M.B., B.Ch., Ph.D. They were not involved with the present study.
“Maria Lehtinen is an innovator in the HSCI community — she’s received one of our Seed Grants for promising early-stage research,” added Woolf. “Her work is a great example of the breadth of different diseases that we study in the HSCI Nervous System Diseases Program.”
Smith R.S. et al. (2018). Sodium Channel SCN3A (NaV1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development. Neuron. DOI: 10.1016/j.neuron.2018.07.052
BCH Vector blog (2018). Gene active before birth regulates brain folding, speech motor development.