Researchers at the Wistar Institute, led by Alessandro Gardini, Ph.D., have made a breakthrough in our understanding of how brain cells, or neurons, develop. Their study, published in the journal Nature Cell Biology, focuses on the role of a specific molecular structure in early neural development. This new knowledge could pave the way for a better understanding of neurodevelopmental disorders.
Dr. Gardini and his team have delved into the intricate processes that occur at the beginning of the nervous system’s development. By doing so, they hope to uncover the root causes of neurodevelopmental disorders and suggest potential solutions. Their research has indicated that the development of neural cells is not solely influenced by transcription factors, as was previously thought.
Each cell in our body contains identical genetic information, yet they are not all the same. Cells receive instructions on what they will become – be it muscle cells, blood cells, or neurons. This transformation begins in the early stages of biological development when stem cells, unspecialized cells with the potential to develop into various mature, specialized cells, start to receive biological signals and inputs.
Dr. Gardini’s research focused on these signals and inputs that guide stem cells to develop into neurons, a process known as “neurogenesis” which includes the formation of the human nervous system and brain. This process isn’t completely understood yet. However, certain mutations in parts of a protein complex called Integrator, known to influence neurogenesis, have been linked to neurodevelopmental disorders.
The team studied the Integrator subunit INST10, finding it to be more abundant in cells from both the central and peripheral nervous systems than other subunits of the same Integrator protein complex. This suggests that neural cells have a vital need for INST10. By using a cell model that replicates early neural development, they discovered that cells with reduced INST10 exhibited different gene-expression signatures and were inclined to develop into a different type of cell, known as mesenchymal cells. This confirmed that INST10 is essential in maintaining the identity of neurons.
When they analyzed individual stem cells, the researchers observed that cells with decreased INST10 lost their “master neuronal genes,” while gaining gene expression signatures consistent with programming for becoming intestinal or smooth-tissue cells. This discovery underscores the critical role of INST10 in preserving the cellular identities of neural cells, both during initial development and throughout the cell’s existence.
