Researchers have discovered information about a gene that sets primates - great apes and humans - apart from other mammals, through the study of a rare developmental brain disorder. They discovered that the PLEKHG6 gene has qualities that drive aspects of brain development differently in primates compared to other species.
"Broadly speaking, this gene can be thought of as one of the genetic factors that make us human in a neurological sense," says the lead author. The senior author says the research, just published in the journal Cell Reports, aimed to address the idea that there must be genes that humans have that have made our brains bigger and better functioning in some respects than other animals. However, that increased complexity could come at a cost, potentially predisposing humans to the development of a whole suite of neurological or psychiatric conditions.
"Such genes have been hard to find, but using an approach where we studied children with a certain brain malformation called periventricular nodular heterotopia, we found a 'damaged' genomic element in a child that had the attributes of such a primate specific genetic factor," the senior author explains. In this particular condition a subset of neurons in the developing brain fail to take up their correct position resulting in a variety of symptoms including epilepsy and delayed development.
The collaborators then set forth to test the point that the gene drives aspects of brain development that are unique to primates. Some amazing data was found using a novel approach through studying human "mini-brains" in culture. It is now possible to take a skin cell and transform it using a set of genetic tricks, so that it can be triggered to form a tiny brain-like structure in culture in the lab.
Their results showed that the particular genetic change that disabled a component of this gene (PLEKHG6) altered its ability to support the growth and proliferation of specialised stem cells in the developing brain. In addition, some of these cells also failed to migrate to their correct position in the growing "mini-brain" during the first few weeks of brain development.
The senior author says it has been known for a while that these stem cells behave differently between primates/humans and other animals, but understanding what genes regulate these differences has been a mystery.
The work also helps provide more information about the list of genes that are altered to cause this particular type of brain malformation.
https://www.eurekalert.org/pub_releases/2018-12/uoo-ord120518.php
https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31775-3
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fa-primate-specific&filter=22
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