Brain cells on the move

The p75NTR protein prevents granule cells from migrating too early to the right location, thereby ensuring the right number of neurons are formed at the right time.

Immunohistochemistry of a mouse cerebellum, showing p75NTR (green), neuronal migratory marker DCX (magenta) and nuclear marker Dapi (blue). Image credit: Zanin and Friedman (CC BY 4.0)

The human brain contains billions of neurons that form vast networks to relay information around the brain and to the rest of the body. The numbers and locations of neurons, and the connections between them, affect how the brain works, so the body carefully controls how, where and when neurons form.

Most of the neurons in the brain arise before we are born from groups of supporting cells known as neuronal precursors. Often, these cells must migrate from one place to another to make neurons in the correction location. For example, neuronal precursors in an area of the embryo brain, called the rhombic lip, produce granule cells – a type of neuron found in the cerebellum, a region of the adult brain that controls our ability to move around. Before making the neurons, the precursor cells first have to migrate out of the rhombic lip into a neighboring area.

Previous studies indicate that a protein known as p75NTR may help to control the ability of brain cells to migrate, but its precise role remained unclear. To address this question, Zanin and Friedman investigated the role of p75NTR in the migration of granule cell precursors in mice and rats.

The experiments found that in animals lacking this protein, the granule cell precursors began to migrate out of the rhombic lip earlier than in normal animals, resulting in excessive numbers of granule cells in the adult cerebellum, which can affect the normal development of an animal. The p75NTR protein appeared to prevent the cells from migrating by activating another protein called RhoA.

Understanding how the body controls when neuronal precursors and other brain cells migrate helps us to understand how the brain develops in healthy individuals and certain neurological disorders, including autism. The next step is to find out whether p75NTR also plays a similar role in the human brain.