Forming and Producing New Neurons

Time-lapse of asymmetric (upper) and symmetric (lower) cell division in the brain of a live zebrafish embryo. Asymmetric cell division allows for production of both neurons and neural progenitors, which are essential for controlling brain growth and differentiation. Symmetric cell division is generally associated with tissue expansion and overgrowth, and it occurs more frequently during the early stages of brain development.

Cell division in a live zebrafish embryo. Paula Alexandre, UCL. Attribution 4.0 International (CC BY 4.0)

Neurons develop through delicate and carefully choreographed processes that take place while an embryo grows. Signaling molecules “turn on” certain genes and “turn off” others, initiating the formation of immature nerve cells. During the next stage — cell division, also called proliferation — the pool of early-stage brain cells increases by billions. Finally, during migration, these newly formed neurons travel to their final destinations. The nervous system formed by these processes is active throughout life, making new connections and fine-tuning the way messages are sent and received.

Formation and Induction

During the very early stages of embryonic development, three layers emerge — the ectoderm (outer-most layer), mesoderm (middle layer), and endoderm (inner-most layer). Although the cells in each layer contain identical DNA instructions for development, these layers ultimately give rise to the rich variety of tissue types that make up the human body. The explanation for this diversity lies in signals produced by surrounding tissues. Those signals turn certain genes on and others off, thus inducing the development of specific cell types. Signals from the mesoderm trigger some ectoderm cells to become nerve tissue, a process called neural induction. Subsequent signaling interactions refine the nerve tissue into the basic categories of neurons or glia (support cells), and then into subclasses of each cell type.

The fate of a developing cell is largely determined by its proximity to various sources of signaling molecules. The concentration of each type of signaling molecule decreases farther from its source, creating gradients throughout the brain. For example, a particular signaling molecule, called sonic hedgehog, is secreted from mesodermal tissue lying beneath the developing spinal cord. As a result of exposure to this signal, adjacent nerve cells are converted into a specialized class of glia. Cells that are farther away are exposed to lower concentrations of sonic hedgehog, so they become motor neurons that control the movement of muscles. An even lower concentration promotes the formation of interneurons, which don’t relay messages to muscles but to other neurons. The mechanism of this molecular signaling is very similar in species as diverse as flies and humans.

Proliferation

In the brain, neurons arise from a fairly small pool of neural stem and progenitor cells, special cells that can divide and become a variety of mature cell types. Before achieving their mature cell fate, this pool of cells undergoes a series of divisions — increasing the number of cells that will ultimately form the brain. Early divisions are symmetric — the split results in two identical daughter cells, both able to keep dividing. But as these divisions progress, the cells begin to divide asymmetrically, giving rise to only one daughter cell that keeps proliferating and a second that progresses towards its ultimate cell fate as a neural or glial cell (the exact sequences and ultimate fates vary by species).

This proliferative process permits rapid growth during early development of the brain, with billions of cells being produced in a matter of weeks. After that series of divisions is complete, only a few neural stem and progenitor cells remain within the brain, and neurogenesis in adulthood is limited to a few regions of the brain, such as those involved with memory.

Scientists have proposed that protein defects causing a premature switch from symmetric to asymmetric divisions may be a cause of microcephaly. This disorder, characterized by a severe reduction in brain size, is associated with serious neurological disabilities and sometimes death in infancy. Similarly, excessive proliferation of brain cells can lead to a disorder called megalencephaly — a brain that is abnormally large and heavy — which is also associated with a variety of neurodevelopmental complications. 

Adapted from the 8th edition of Brain Facts by Lindzi Wessel.

About the Author

Lindzi Wessel

Lindzi Wessel is a freelance science journalist who graduated from the UC Santa Cruz Science Communication Program. Before turning her sights on journalism, she studied the mind, obtaining a bachelor’s degree in psychology and a master’s in neuroscience from UC Davis. For the moment, she resides in Santiago, Chile, where she’s learning about science coming out of South America.