Researchers identify and map a previously unknown gene critical for human brain development.
Compared to other mammals, humans have the largest cerebral cortex. A sheet of brain cells that folds in on itself multiple times in order to fit inside the skull, the cortex is the seat of higher functions. It is what enables the person to process everything they see, hear and think and it is the expansion of the cerebral cortex which sets humans apart from the rest of their fellow primates. However, researchers have long wondered what mechanisms are responsible for this evolutionary development. Now, a study from researchers at UC Santa Barbara has pinpointed a specific long non-coding ribonucleic acid (lncRNA) that regulates neural development (ND). The team state that this lncND can be found only in the branch of primates that leads to humans, in a stretch of nucleotides that does not code a protein, and is turned on during development and turned off when the cell matures. The opensource study is published in the journal Neuron.
Previous studies show that lncRNAs have complex and diverse functions in brain development. lncRNAs have relatively low levels of evolutionary conservation with sequence deletions and insertions and accelerated nucleotide substitution at evolutionary divergences. About a third of the lncRNAs are unique to the primate lineage and only 12% of human lncRNAs appear to be conserved in other vertebrate species. The current study provides evidence for the involvement of lncRNA, termed LncND (neurodevelopment) in primate brain expansion.
The current study identifies several binding sites on lncND for another type of RNA called a microRNA, one of them, called microRNA-143, binds to lncND. Results show that lncND could sequester this microRNA and in doing so regulate the expression of Notch proteins. The lab explain that notch proteins are very important regulators during neuronal development. Data findings show that LncND is expressed in neural progenitor cells and then declines in neurons.
The group explain that lncND is a platform that binds microRNAs like a sponge, which allows Notch to do what it's supposed to do during development. They go on to add that as the brain matures, levels of lncND then go down and when they do, those microRNAs come flying off the platform and attach to Notch to bring its levels down; it is in this way that Notch levels are kept high while the brain is developing and lowered once maturation occurs.
The team surmise that their work identifies a very critical gene for human brain development and a component that likely contributes to brain expansion in humans. For the future, the researchers state that their findings suggest a molecular mechanism by which the emergence of LncND in primates and its co-evolution with a highly conserved miRNA-143-3p contributed to the expansion of radial glia in higher primates.
This is an immunostaining after two weeks of differentiation of neural progenitor cells into neurons. Credit: Neha Rani.