# Investigating the role of a conserved serine/threonine kinase, SAX-1, in higher-order dendrite pruning

> **NIH NIH F31** · YALE UNIVERSITY · 2022 · $46,752

## Abstract

PROJECT SUMMARY
Neurite remodeling is a highly conserved process that refines and establishes a mature nervous system. A failure
in neurite remodeling leads to neurological and neurodevelopmental disorders. While developmental dendritic
pruning, a means of neurite remodeling, has been extensively studied, the cell-biological mechanisms that
control pruning remain poorly understood. Specifically, there is a fundamental gap in understanding how neurons
can selectively prune specific dendritic branches while leaving sister branches intact. The long-term goal is to
identify and understand the cell-biological mechanisms that direct branch-specific pruning. The nematode
Caenorhabditis elegans inner labial 2 (IL2) neurons, upon entering a developmental diapause, extend a
stereotypical dendritic arbor that is pruned when development is resumed – leaving primary dendrites intact. The
stereotypic remodeling of IL2 neurons allows experimental access to elucidate the cell-biological mechanisms
that confer selective pruning. The central hypothesis is that SAX-1, an evolutionarily conversed serine/threonine
kinase, functions in a molecular pathway that links calcium signaling to cytoskeletal dynamics in higher-order
dendrite branches to direct selective pruning. The rationale for this proposal is that studying the role SAX-1
during IL2 remodeling will offer a framework to understand how local regulation of the cytoskeleton confers
branch-specific pruning. The central hypothesis will be tested by the following specific aims: 1) determine how
SAX-1 directs pruning of higher-order IL2 dendrite branches; and 2) identify the genetic pathway in which SAX-
1 acts to regulate the cytoskeleton during pruning. The research proposal is innovative because it will 1) be the
first to establish C. elegans as a model system for studying pruning, 2) elucidate a novel role for SAX-1 in
dendritic pruning, and 3) determine how the cytoskeleton is locally regulated during pruning. The proposed
research is significant because elucidating the fundamental cell-biological mechanisms of branch-specific
pruning will significantly advance our understanding of developmental neurite remodeling. This understanding is
a critical to inform us about how neurodevelopmental processes go awry in disorders such as Down Syndrome.

## Key facts

- **NIH application ID:** 10537345
- **Project number:** 1F31NS122294-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Paola V Figueroa-Delgado
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-01-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537345

## Citation

> US National Institutes of Health, RePORTER application 10537345, Investigating the role of a conserved serine/threonine kinase, SAX-1, in higher-order dendrite pruning (1F31NS122294-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10537345. Licensed CC0.

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