Defining the function of a novel insulin-like growth factor binding protein in CNS development and function
Active Project Grant Awarded Last action
- Award ID
- F31NS139448
- Recipient
-
Case Western Reserve University UEI HJMKEF7EJW69
- Awarding agency
-
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Department of Health and Human Services
- Obligated
- $167,602
Award facts
- Assistance listing
- 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
- Completion date 71% complete
- Place of performance
- Cleveland, OH 44106, USA
Award details come from USAspending.gov.
Description
- 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 tuneactivity 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 andregulation 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 tunessignaling 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 onactivity/IIS. These studies will provide novel mechanistic insight into the regulatory mechanisms governingactivity 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.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $38,800 | |
| Amendment | $43,310 | |
| Amendment | $42,746 | |
| Amendment | $42,746 | |
| Original award | $0 |
Quick answers
Who received award F31NS139448?
F31NS139448 was awarded to Case Western Reserve University by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on January 6, 2025.
How much is award F31NS139448 worth?
$167,602 has been obligated on F31NS139448.
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