# In vitro approaches to study human cerebellar development

> **NIH NIH R21** · SEATTLE CHILDREN'S HOSPITAL · 2024 · $478,732

## Abstract

PROJECT SUMMARY
The human cerebellum despite its small size relative to the cerebral cortex, contains nearly 80% of all neurons
in the brain. While it is classically associated with motor function, recent studies indicate a role for the human
cerebellum in higher cognitive functions such as speech, language and even satiety. Cerebellar disease,
including malformations and tumors, are common. Yet, our understanding of the cellular and molecular basis of
cerebellar disease is poor. One reason for this could be our animal model-centric view of normal and abnormal
cerebellar development. We have identified several unique cerebellar developmental features in human that
are absent in commonly studied animal models, including rodents and non-human primates like the macaque.
These features include spatiotemporally expanded progenitor zones, like the rhombic lip that produces
cerebellar glutamatergic neurons and an expanded ventricular zone that produces GABAergic neurons. The
rhombic lip in humans is also long-lived and undergoes a series of morphological and cellular changes that are
yet to be identified in other animal species. The presence of human-specific features of normal human
cerebellar development partly explains why modeling cerebellar disease in animals has been a challenge. This
study aims to characterize the cellular features of these expanded progenitor zones in human using a battery
of in vitro assays, including live imaging microscopic protocols that measure the proliferative and migratory
characteristics of cells residing in these stem cell zones. We will also conduct rigorous single-cell
transcriptomic and epigenomic analyses of this progenitor zones to define the molecular pathways driving its
development. This study leverages our extensive expertise of cerebellar development in human and other
animal models, together with our unique access to fresh normal human fetal tissue obtained at the University
college London through the Human Developmental Biology Resource.

## Key facts

- **NIH application ID:** 10951406
- **Project number:** 1R21NS138661-01
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Parthiv Haldipur
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $478,732
- **Award type:** 1
- **Project period:** 2024-07-16 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10951406

## Citation

> US National Institutes of Health, RePORTER application 10951406, In vitro approaches to study human cerebellar development (1R21NS138661-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10951406. Licensed CC0.

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