During brain development, newly formed neurons journey to their designated place to form functional circuits, a process called neuronal migration. One mode of this movement is tangential migration, where neurons travel parallel to the brain’s surface. This is like cells taking a cross-country trip to settle in their permanent homes, moving laterally across the developing landscape rather than directly outward.
The Cellular Journey
The journey for many tangentially migrating neurons begins in “birthplaces” deep within the developing brain, primarily a region known as the ganglionic eminences. From this starting point, a class of neurons known as inhibitory interneurons begins its extensive trek. These interneurons navigate through a complex environment along specific pathways within the embryonic brain. Their destination is the cerebral cortex, the brain’s outer layer responsible for higher cognitive functions, where they integrate into distinct layers.
Contrast with Radial Migration
While tangential migration involves a sideways journey, another mode of cell movement called radial migration occurs simultaneously. Radial migration is a direct, “climbing” motion where neurons move from their birthplace perpendicularly toward the brain’s surface. These neurons use the long fibers of specialized cells, known as radial glia, as scaffolding to guide their ascent.
To visualize the difference, imagine a building under construction. Radial migration is like workers climbing a ladder from the ground floor to a higher level. In contrast, tangential migration is like workers walking horizontally across the beams of a single floor. Both forms of migration work in concert to assemble the brain’s cellular organization.
Molecular Navigation Signals
A neuron’s ability to navigate the path of tangential migration depends on a cellular guidance system that functions like a biological GPS. This system uses molecular signals to create pathways and boundaries that migrating neurons follow. The process relies on two opposing types of cues: chemoattraction, which involves molecules that attract the neuron, and chemorepulsion, which involves molecules that repel the cell from certain areas.
Several families of proteins act as these guidance cues, including Slits, Semaphorins, and Netrins, functioning as the “stop” and “go” signals of the developing brain. For instance, a neuron might be repelled by a Semaphorin signal to steer it from an incorrect path, while being attracted by a Netrin signal from its target destination. This interplay of push-and-pull forces ensures neurons follow their prescribed routes.
The migrating neuron is an active participant in this process. Its leading edge, a dynamic structure called the growth cone, is equipped with receptors that detect these molecular signals. The growth cone constantly samples its surroundings, and upon binding to guidance cues, it triggers internal changes within the neuron that control the direction of movement.
Building a Balanced Brain
The purpose of this migratory journey is to establish a balance between different types of neural activity. Brain circuits are composed of excitatory neurons that generate “go” signals and inhibitory neurons that provide “stop” signals. Tangential migration is the primary mechanism for distributing inhibitory interneurons throughout the cerebral cortex, where they integrate into circuits dominated by excitatory neurons.
A car provides a good analogy, as it requires both an accelerator (excitatory) and a brake (inhibitory) to operate safely. Without inhibition, brain circuits would be prone to over-activation, like a car with a stuck accelerator. This balance between excitation and inhibition allows for complex information processing, preventing runaway signaling and enabling the refined computations that underlie brain function.
When Migration Goes Awry
Errors in tangential migration can have significant consequences for brain function. If the molecular navigation system fails or cells cannot respond to guidance cues, neurons may not reach their intended destinations, disrupting the balance of excitatory and inhibitory cells. For example, a localized deficit of inhibitory interneurons can leave a brain region without enough “stop” signals, contributing to several neurodevelopmental conditions.
A reduced number of inhibitory neurons in the cortex can lower the seizure threshold, as circuits become hyperexcitable, a factor in some forms of epilepsy. Misplaced interneurons can also lead to disorganized communication within and between brain regions, a feature observed in disorders like schizophrenia and certain forms of autism spectrum disorder. While these conditions are multifaceted, with genetic and environmental factors also playing a role, disruptions in tangential migration represent an underlying biological mechanism that can contribute to their development.