Which way to the brain?

Experiments in the embryos of zebrafish shed new light on how immune cells called microglia find their way to the retina in the brain during development.

Microscopy image showing microglia (pink) infiltrating the retina of a zebrafish embryo by interacting with retinal neurons (green). Image credit: Nishtha Ranawat (CC BY 4.0)

The immune system is comprised of many different cells which protect our bodies from infection and other illnesses. The brain contains its own population of immune cells called microglia. Unlike neurons, these cells form outside the brain during development. They then travel to the brain and colonize specific regions like the retina, the light-sensing part of the eye in vertebrates.

It is poorly understood how newly formed microglia migrate to the retina and whether their entry depends on the developmental state of nerve cells (also known as neurons) in this region. To help answer these questions, Ranawat and Masai attached fluorescent labels that can be seen under a microscope to microglia in the embryos of zebrafish. Developing zebrafish are transparent, making it easy to trace the fluorescent microglia as they travel to the retina and insert themselves among its neurons.

Ranawat and Masai found that blood vessels around the retina act as a pathway that microglia move along. Once they reach the retina, the microglia remain attached and only enter the retina at sites where brain cells are starting to mature in to adult neurons. Further experiments showed that microglia fail to infiltrate and colonize the retina when blood vessels are damaged or neuron maturation is blocked.

These findings reveal some of the key elements that guide microglia to the retina during development. However, further work is needed to establish the molecular and biochemical processes that allow microglia to attach to blood vessels and detect when cells in the retina are starting to mature.