Tracking the Brain’s Secret Agents: A New Look at Zdhhc22 Palmitoyltransferase

Imagine a sprawling metropolis under a total blackout. You need to locate a specific network of secret agents operating within the city. You cannot see the agents themselves; they are invisible to the naked eye. So, you hack the electrical grid. You rig the system so that the moment an agent enters a safehouse and unlocks the door, the windows of that specific building flood with a brilliant crimson light.

You do not need to see the spy. You only need to track the red windows. If a skyscraper glows on the east side, you know the operation has moved there. If the lights go out and reappear downtown, you know the agents have relocated.

In this recent lab study, scientists applied this precise logic to the mammalian brain. The invisible agent is Zdhhc22 palmitoyltransferase, a protein suspected of helping neurons decide what they want to be when they grow up. To track it, the team created a transgenic mouse. They inserted a piece of genetic code—a bacterial artificial chromosome—that acts like the rigged electrical grid. Whenever the mouse's DNA gives the order to produce Zdhhc22, it simultaneously produces mCherry, a protein that glows red under a microscope.

Illuminating Zdhhc22 palmitoyltransferase pathways

The resulting imagery provided a dynamic map of brain construction. The researchers did not see a static picture; they saw a shifting pattern of activity.

If you observed the brain at embryonic day 13.5, the red lights were not scattered randomly. They were strictly organised at the brain’s outer rim, known as the marginal zone. This suggests the protein is vital for the early stages of brain development. These glowing cells were identified as Cajal-Retzius cells. Think of them as the site foremen who arrive first to lay out the blueprints for the cortex.

But the pattern changes. If you fast-forward to embryonic day 17.5, the red glow expands. It sinks into the deeper layers of the cortex. By the time the mouse is born, the agents have established a permanent residence in these deep layers.

From observation to implication

The study measured exactly which cells were glowing. Through co-immunostaining—a method of chemically tagging specific cell types—they confirmed the red light was almost exclusively inside neurons. The support staff of the brain, the glial cells, remained dark.

If Zdhhc22 is absent from glia but abundant in neurons like those in Layer VI, then its function is strictly tied to neuronal machinery. It is not a general maintenance protein; it is a specialist.

This new mouse line serves as a validated tool. Because the mCherry reporter faithfully mimics the natural expression of the gene, scientists can now use this model to manipulate the protein. They can turn the lights on and off to see what happens to the brain's architecture. The map is drawn; now the exploration begins.