UCLA researchers have identified the regulatory network that controls the transformation of neuronal progenitor cells into movement nerve cells in chicken and mouse embryos.
The study adds insight into the development and functioning of spinal movement nerve cells. It also may contribute to the production of stem cell-derived movement nerve cells in the laboratory. Scientists may be able to use the cells to treat several diseases, including ALS and spinal muscular atrophy.
Researchers reported their discoveries in an article titled “Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics” in the journal PLOS Biology.
“This study provides an unprecedented detailed view of how embryos produce the different cell types found in the mature spinal cord,” Bennett Novitch, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, said in a news release. “The new experimental techniques we used, combined with collaborative efforts of biologists and computer scientists, are allowing us to gain new insight into the exquisite accuracy of embryonic development,” said Novitch, the study’s senior author.
During embryonic development, tissue formation and organization rely on tightly regulated networks that control patterns of genetic expression, tissue growth, and cell differentiation. This is also true for the formation of the spinal cord and its different types of nerve cells, because all derive from precursor stem cells called neural progenitors.
Taking advantage of advanced molecular techniques, researchers at UCLA and the Francis Crick Institute in London evaluated the development regulatory network in about 200 single neural progenitor cells that were on their way to becoming movement nerve cells. Using software they developed, they identified a gene called Olig2 as a master regulator of movement nerve cell development.
The team first learned that Olig2 is present only in neural progenitors that will develop into mature movement nerve cells. Another discovery was that Olig2 can trigger several signaling pathways that determine the cells’ final fate. In addition, the team learned that the protein that the Olig2 gene generates promotes movement nerve cell development by suppressing the activity of other genes. These Hes genes curb nerve cell differentiation.
The researchers confirmed Olig2’s role in promoting movement nerve cell formation by studying chicken and mice embryos. When the team genetically prevented the production of Olig2, neural progenitor cells were unable to give rise to movement nerve cells.
“During embryonic development, the nervous system is constructed following a precise blueprint, with key parts forming at precise times and places, and appropriate numbers,” said Novitch, who is also UCLA’s Ethel Scheibel Professor of Neurobiology. “Our research sheds light into how this process is orchestrated specifically for motor neuron [movement nerve cell] development.”