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How do neural stem cells form neurons and glial cells?

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Diagram showing the locations of neural stem cells in brain regions such as the hippocampus and ventricles, and hematopoietic stem cells in the bone marrow and blood, with labeled illustrations of the brain, spinal cord, circulatory system, and skeleton. — stem cell Stem cells of neural and hematopoietic origin have tremendous potential in the development of therapies for certain diseases, such as diabetes and Parkinson disease. Neural stem cells occur in the spinal cord and in specific regions of the brain, and hematopoietic stem cells occur in the blood and bone marrow.

Neural stem cells (NSCs) are undifferentiated cells within the central nervous system that possess the potential to develop into neurons and glial cells. The process by which these cells differentiate is complex and regulated by the specialized microenvironment, or niche, in which they reside.1

A key mechanism governing this differentiation is lateral inhibition, which allows a population of precursor cells to generate diverse cell types. In the developing vertebrate central nervous system, cells within the neuroepithelium utilize surface molecules known as Notch and Delta to communicate with adjacent cells.2

Neuronal Differentiation: When a cell expresses high levels of Delta, it activates the Notch receptor on neighboring cells. This activation triggers an intracellular cascade that suppresses neuronal differentiation in those neighbors. Consequently, the cell with high Delta production is directed to develop into a neuron.2
Glial Differentiation: Conversely, cells that experience high Notch activation—due to the influence of Delta from their neighbors—are inhibited from becoming neurons. These cells instead remain as precursor cells or differentiate into glial cells, which provide structural and functional support to neurons.12

While scientists have identified these pathways, they are still working to fully understand how to control the proliferation, migration, and survival of NSCs and their progeny for therapeutic applications.1