# Defining the function of a novel insulin-like growth factor binding protein in CNS development and function

> **NIH NIH F31** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $42,746

## Abstract

PROJECT SUMMARY/ABSTRACT
Across the animal kingdom, specialized neurosecretory cells coordinate endocrine and central nervous system
signals to construct neural circuits and maintain homeostasis. Insulin/insulin-like growth factors (IGFs) are key
secreted neuropeptides whose signaling activities are strictly regulated by IGF-binding proteins (IGFBPs).
Despite misregulated insulin/IGF signaling (IIS) being linked to the pathogenesis of neurodevelopmental
disorders, the cellular and molecular mechanisms by which IGFBPs precisely tune IGF activity in the brain to
sculpt neural circuits and modulate behavioral outputs are largely undefined. The Drosophila system provides
an appealing model to address these questions given only two IGFBPs are encoded in the fly genome, Imp-L2
and Crimpy. Our lab discovered Crimpy and defined its role in facilitating TGFβ signaling at the peripheral
neuromuscular junction, but its roles in the central brain and IGF regulation are completely unexplored. Our
preliminary data suggest that Crimpy is required for axon morphogenesis and circuit formation of the
mushroom body, the fly learning and memory center. We also demonstrated that Crimpy is required to promote
wild-type sleep behavior. Notably, Crimpy’s cellular requirements for axon morphogenesis and sleep regulation
were mapped to a cluster of 14 neurosecretory cells at the brain midline, termed insulin producing cells (IPCs),
which produce and secrete insulin-like peptides/IGFs. Based on these results, we hypothesize that Crimpy
tunes IGF signaling from IPCs to promote proper central brain circuit development and function.
Through the use of innovative genetic schemes, immunocytochemistry, as well as behavioral and
electrophysiological analyses, this proposal seeks to: 1) establish roles for Crimpy in IPCs for central brain
morphogenesis and circuit formation, 2) assess Crimpy’s function in IPCs to promote wakefulness, and 3)
define Crimpy’s regulatory actions on IGF activity/IIS. These studies will provide novel mechanistic insight into
the regulatory mechanisms governing IGF activity to fill fundamental gaps in our understanding of IIS in
constructing neural circuits and modulating behavior. In addition, these proposed goals and approaches will
provide exceptional training opportunities to strengthen my technical and professional skills, and prepare me
for independence as I advance in my scientific career.

## Key facts

- **NIH application ID:** 10994420
- **Project number:** 1F31NS139448-01
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Jerrik Rydbom
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $42,746
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10994420

## Citation

> US National Institutes of Health, RePORTER application 10994420, Defining the function of a novel insulin-like growth factor binding protein in CNS development and function (1F31NS139448-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10994420. Licensed CC0.

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