New neurons appeared after brain injury in a transparent adult fish

New neurons appeared after brain injury in a transparent adult fish

On October 29, Science published a whole-body cell atlas of the fish Danionella cerebrum. A team at the Whitehead Institute for Biomedical Research examined gene activity in more than 600 thousand cells collected from multiple adult fish.

In 2018, the same laboratory created a similar map for a planarian, a flatworm that can regrow lost body parts. Danionella's small size, about 12 millimeters in length, helped the researchers apply this method to an adult vertebrate. Its brain can be viewed from above: the bones of the skull roof are absent, leaving only skin covering the brain.

The researchers isolated cells from different parts of the body and used their RNA to identify which genes were active. They grouped cells with similar patterns of gene activity. By labeling RNA from selected genes in tissue sections, they could see where different cell types were located and which cells were next to them.

In adult fish, connective tissue cells called fibroblasts continued to express genes that establish the arrangement of body parts in the embryo. Genes associated with forelimb development in other vertebrates were active in the pectoral fins, while genes associated with hindlimb development were active in the pelvic fins. The authors suggest that this “positional memory” may help adult tissue maintain and restore the structure appropriate to its location in the body.

To follow brain repair, the researchers compared cell states after injury with the healthy tissue atlas. They injured one side of the telencephalon, a brain region involved in learning and memory. They compared cells from different fish at 12 hours and 3, 7, 14 and 30 days after injury. Gene activity revealed a sequence: an early wound response involving immune cells, followed by the division of radial glia, cells that give rise to new neurons in fish, and then neuronal maturation.

In a separate experiment, on the third day after injury, the fish received a labeling substance for 24 hours that becomes incorporated into DNA as it is copied. On day 26, the researchers found mature neurons carrying this label on the injured side. These neurons were descendants of cells that had synthesized DNA shortly after injury.

The uninjured side of the brain also responded to the injury. Gene activity related to metabolism and the stress response changed on that side. The researchers compared both sides with the same brain region in uninjured fish, allowing them to identify changes beyond the wound and distinguish them from the local response.

The publicly accessible map can help researchers choose which cells to target, and when after injury to target them, in a subsequent experiment testing their role in repair.