cerebellar granule cell precursor tangential migration

Definition

Target type: biologicalprocess

The early migration of granule cell precursors in which cells move orthogonal to the direction of radial migration and ultimately cover the superficial zone of the cerebellar primordium. [GO_REF:0000021, GOC:cls, GOC:dgh, GOC:dph, GOC:jid, PMID:15157725]

Cerebellar granule cell precursor (GCP) tangential migration is a critical process for the development of the cerebellar cortex. GCPs are born in the external germinal layer (EGL), a proliferative zone located at the periphery of the cerebellum. These cells migrate tangentially, meaning they move parallel to the pial surface, across the cerebellar surface to reach their final destination in the internal granule layer (IGL). This journey is crucial for building the functional circuitry of the cerebellum.

During tangential migration, GCPs undergo several steps:

1. **Proliferation and Birth:** GCPs are generated through mitosis in the EGL. They are initially undifferentiated cells with high proliferative potential.

2. **Migration Initiation:** GCPs receive signals from various sources that trigger their migration. These signals include guidance cues like netrin-1, Slit2, and Ephrin-A5, which are expressed in specific locations within the cerebellar cortex.

3. **Tangential Movement:** GCPs move across the cerebellar surface, guided by the guidance cues mentioned above. They extend filopodia, which are thin, actin-rich projections that sense the surrounding environment and help guide migration.

4. **Migration Pathway:** The migration pathway is not random. GCPs follow specific routes, often forming streams or chains of migrating cells. This organized movement ensures that they reach their correct location in the IGL.

5. **Stopping and Differentiation:** Upon reaching their destination in the IGL, GCPs stop migrating and begin to differentiate into mature granule cells. They develop their characteristic morphology, express specific markers, and integrate into the cerebellar circuitry.

This process of GCP tangential migration is crucial for the following reasons:

- **Formation of the Cerebellar Cortex:** The migration of GCPs contributes to the layered structure of the cerebellar cortex, creating the IGL, which is the major site of cerebellar output.

- **Circuit Formation:** The positioning of granule cells in the IGL allows them to form synapses with other cerebellar neurons, including Purkinje cells and interneurons, enabling complex cerebellar function.

- **Functional Development:** The timing and accuracy of GCP migration are crucial for the proper development of cerebellar circuits and functions, including motor control, coordination, and learning.

Disruptions in GCP tangential migration can lead to cerebellar malformations and developmental disorders that affect motor function and learning. Understanding the mechanisms regulating this process is essential for developing therapies for such disorders.'
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