# Sculptors of cerebellar fissures and their potential as therapeutic targets for cerebellar dysfunction

## TL;DR

This paper reviews how specific signaling pathways shape cerebellar development and explores BDNF's role in treating cerebellar dysfunction.

## Contribution

The paper highlights BDNF signaling as a novel therapeutic target for cerebellar developmental disorders.

## Key findings

- BDNF signaling is critical for cerebellar foliation and its disruption leads to hypoplasia.
- Restoring BDNF signaling may reverse developmental cerebellar disorders.
- Autism spectrum disorder is partially linked to vermal lobule hypoplasia via BDNF/TrkB signaling.

## Abstract

The cerebellum plays an important role in both motor control and cognition. The cerebellar cortex is neuron-rich and composed of characteristic folia and fissures. Defective cerebellar development leads to movement disorders and developmental delay. During early morphogenesis, cellular signaling programs orchestrate simultaneous cerebellar growth and foliation. Aberrant signaling causes various degrees of cerebellar hypoplasia. Based on mouse genetic studies, we discuss several developmental signaling pathways that drive cerebellar morphogenesis. Notably, hypoplasia of vermal lobules VI-VII has been linked to autism spectrum disorder and is in part attributed to brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B signaling. This review also discusses how BDNF biogenesis is critical for cerebellar foliation and whether restoring BDNF signaling could reverse cerebellar developmental disorders.