neuroscience researchers identified a critical gene for brain development and figuring out how it works ;
Compared to other mammals, humans have the largest cerebral cortex. A sheet of brain cells that folds over itself several times in order to fit inside the skull, the cortex is the seat of higher functions. It is what allows us to process everything we see and hear and think.
Expanding the cortex brain differentiates humans from the rest of their fellow primates. However, scientists have wondered what mechanisms are responsible for this evolutionary development.
New research from the Molecular Neurobiology and Cell Kosik Laboratory University of California, Santa Barbara has identified a long nocoding specific ribonucleic acid (lncRNA) regulating neuronal development (ND). The results appear in the journal neuron .
“This lncND, as we called, can be found only in the branch of primates leading to humans. It is a stretch of nucleotides that does not encode a protein,” said lead author Kenneth S. Kosik, Harriman professor of Neuroscience Research at the Department of Molecular Biology, cell and Developmental Biology at UCSB. “We showed that lncND lights off during development and when the cell matures.”
Lead author Neha Rani, a postdoctoral scholar in the laboratory Kosik, idenfitied several binding sites in lncND for another type of RNA called microRNA. One of them, called microRNA-143, joins lncND.
“We found that microRNA lncND could hijack this and in doing so, regulate the expression of Notch proteins,” Rani said. “Notch proteins are important regulators during neuronal development. They are involved in cell differentiation and cell fate and are fundamental in the way of neuronal development.”
lncND Kosik described as a platform linking these microRNAs like a sponge. “This allows Notch to do what you have to do during development,” he said. “Then, as the brain mature, levels of lncND down and when they do, microRNAs come flying platform and wrap the Notch to bring your levels down. He wants levels of Notch to be high while the brain is developing but not once maturation occurs. This lncND is an elegant way to change the levels of Notch quickly. ”
To replicate these results in cell culture, Rani used to grow human stem cells neurons in what is called a mini brain. In this small gob of brain tissue , a subpopulation of radial glia-cells (neural stem cells) and other neural-responsible parents do lncND identified.
However, the researchers wanted to see the radial glial cells in the actual tissue human brain , so they returned to their colleagues in Development and Graduate Program stem cell biology at the University of California San Francisco School of Medicine. Using in situ hybridization, UCSF scientists found lncND in neural precursor cells but not in mature neurons.
“It was right where we thought it would in the brain tissue,” Kosik, who is also the co-director of the Neuroscience Research Institute at UCSB said. “But I still had one more thing we had to do because people still would not be satisfied that we had done everything possible to show that lncND was really doing something functionally.”
So the UCSF team lncND introduced into the brain of the developing fetus of a mouse. green fluorescent protein labeling allowed to see the development pattern of the first and prove that lncND, which is not normally present in mice lncND is present only in some primates, including humans had-a functional effect on development.
“When lncND overexpressed in mouse fetus, which actually affects the development as planned,” Kosik said. “The pattern of early development moves towards more precursor cells, even though the mouse does lncND at all.”
According to Kosik, this work not only identified a critical gene for brain development, but also provides a clue to a component that probably contributed to the expansion of the brain in humans. “We have shown that lncND could be an important step in the expansion of the human brain, which is interesting in itself player,” Rani said. “Another interesting aspect of this work is that lncND appears to help regulate the pathway of Notch signaling key development.”
This article was originally published on medicalxpress, Read the original article
Posted in: Neuroscience