Researchers Discover How Neurons Wire Brain in Embryos

Jasmin Wu/UCSD Guardian

Researchers have discovered how nerves wire the brain during embryonic development. The findings provide insight into generating new therapies for spinal cord injury patients suffering from nerve damage.

Using spinal tissue from mice embryos about 11 days into gestation, neurobiology associate professor Yimin Zou and his research team uncovered how nerve pathways are paved during the early stages of development, when cells disperse to specific regions to form the nervous system. Until now, people didn’t know how neurons moved and which chemical signals helped them.

The neuron movements are caused by growth cones, which are highly sensitive and motile structures located at the tips of growing nerves. The growth cones use Wnt proteins, which act as the molecules that move the neurons by creating a signal called planar cell polarity (PCP).

Although growth cones find their destinations by reacting to varying chemical cues in the developing nervous system, no one knew how they responded to the different chemical concentrations.

The findings also indicate the importance of the molecule Vangl2 — used in PCP to help the growth cone develop —  in leading the axon toward its target. The molecule is highly concentrated in the filopodia, which make up the tips of the growth cones.

“This suggests that the tips of the growth cone at the filopodia are the most sensitive part of the growth cone,” Zou said. “It is not the entire growth cone that is evenly sensitive.”

The research shows that Vangl2 responds to the signals created by the Wnt protein, which tells the growth cone where to move.

“While the growth cone is turning in a certain set of directions, the axon will grow longer, [which leaves] behind neuronal connections,” Zou said.

The pathways neurons use to develop can be used in therapies for spinal cord injury patients.

During severe spinal cord injury, neurons that allow for sensory input and motor output are damaged, and patients lose sensation and movement below the affected area.

“After axons are damaged, they can no longer regrow, and we get paralysis,” Zou said.

The axon guidance system can be used to help neurons grow by using the Wnt signaling mechanism to try and repair axons after spinal cord injury, for both sensory and motor systems

“Once development is over, these axon guidance systems are temporarily put to rest — they are not working anymore,” Zou said. “But if there is traumatic injury to the spinal cord, they can quickly re-induce those guidance systems.”