# Characterizing human-specific expression of ZP2 in the cerebellum

> **NIH NIH F30** · YALE UNIVERSITY · 2022 · $31,608

## Abstract

SUMMARY
 Finding new treatments for neuropsychiatric disorders is a priority, as these disorders affect over
1 in 5 US adults and cost the US health care system over 180 billion dollars annually. Challenges
limiting the pursuit of new treatments include 1) issues associated with using animals to model higher
cognitive behaviors and 2) the implication of disparate brain regions that, when disrupted, manifest in
diverse symptoms in motor, affective, and cognitive domains. To address these issues, this proposal
will characterize the expression and deletion-associated phenotypes of a gene, ZP2, that exhibits
human-specific expression in the cerebellum. The cerebellum has recently been implicated in
coordinating higher cognitive functions, and its disruption has been associated not only with motor but
also with cognitive and affective symptoms. In a comprehensive transcriptomic study of the brain,
examining differential gene expression between humans and primates, the Sestan lab discovered that
ZP2, a protein canonically involved in stabilizing the extracellular matrix and preventing polyspermy at
the mammalian oocyte, is also uniquely expressed in human cerebellum. This proposal will investigate
a potential analogous role of ZP2 at the granule cell dendrite, where it is hypothesized that ZP2 anchors
and guides mossy fiber interactions during synaptogenesis and development. To do so, this proposal
includes utilizing postnatal post-surgical and post-mortem human brain tissue and differentiated human
induced pluripotent stem cells as a model system to localize ZP2 expression, determine ZP2 binding
partners, and determine whether ZP2 is mechanistically implicated in the development of synapses
between cerebellar granule cells and mossy fibers. This work has the potential to shed light on
mechanisms of synaptic development that may be unique to humans and a potential molecular target
for human-specific cognitive functioning localized to the cerebellum. This application also includes a
training plan that will prepare the applicant for a career investigating neurodevelopmental disorders as
a clinician-scientist.

## Key facts

- **NIH application ID:** 10316165
- **Project number:** 5F30MH123074-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Adriana Cherskov
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $31,608
- **Award type:** 5
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316165

## Citation

> US National Institutes of Health, RePORTER application 10316165, Characterizing human-specific expression of ZP2 in the cerebellum (5F30MH123074-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10316165. Licensed CC0.

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