# Role of semaphorin signaling in neuronal recovery from dendritic injury: a comparative case study in-vitro and in-vivo

> **NIH NIH R15** · NEW JERSEY INSTITUTE OF TECHNOLOGY · 2022 · $454,319

## Abstract

Both axons and dendrites are damaged during traumatic brain injury and Spinal Cord Injury, causing a loss of
synaptic connectivity and neural network breakdown. Yet, most studies of neural regeneration focus on axons,
leaving dendritic responses to injury vastly unexplored. It is unknown whether and how dendrites reestablish
themselves, influence axonal regeneration, or even promote circuit reconnection. The proper patterning of axons
and dendrites during development, and regeneration, rely heavily on the precise morphogenesis of these
processes, which in turn relies on guidance molecule signaling. Here we focus on semaphorins and their
receptors, the plexins and neuropilins. Evolutionary conserved, the semaphorin signaling pathways are crucial
to the establishment of neural circuits from invertebrates to vertebrates during development but their involvement
in response from injury is unknown.
Our long-term goal is to determine the network, cellular, and molecular mechanisms that affect recovery from
injury. Our central hypotheses are that soluble semaphorins promote dendritic proliferation after injury, similar to
their role during development, while membrane-bound semaphorins are limiting factors that need to be overcome
to allow dendritic proliferation as well as synaptic formation. Here we set out to determine the shared fundamental
mechanisms in dendritic response to injury by leveraging the in-vivo approach using the invertebrate C. elegans,
with in-vitro methods based on mouse primary neuronal culture.
We will use a femtosecond-pulse laser to precisely disconnect individual dendrites of neurons in live, behaving
nematode and in a primary culture of mouse cortical neurons. For each of these complimentary model systems
we adapted a microfluidic device that will improve control of ligand application and survivability. We will then test
the roles of different semaphorins and plexins in response to dendritic transection by using C. elegans knockout
strains for their genes, as well as transgenic overexpression and siRNA to regulate the protein levels, and
application of synthetic Sema3A ligand and siRNA on mouse neurons. We will assay the time course of
morphological changes, synaptogenesis, neuronal activity in individual cells and the corresponding circuit, as
well as functional recovery of connections.
Together, these aims will examine, both in-vitro and in-vivo, roles of semaphorin signaling in neuronal response
after dendritic injury. Our anticipated results will uncover cellular and network mechanisms that share a molecular
signaling pathway. The proposed research will be carried out by a talented PhD candidate and several mentored
undergraduate students at the New Jersey Institute of Technology. We will recruit motivated, diverse, and
capable students, and encourage their curiosity and supporting their career goals. The skills and methods that
the participating young scientists will acquire will increase their desirability for the next ste...

## Key facts

- **NIH application ID:** 10358797
- **Project number:** 1R15NS125565-01
- **Recipient organization:** NEW JERSEY INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Gal Haspel
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $454,319
- **Award type:** 1
- **Project period:** 2021-12-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10358797

## Citation

> US National Institutes of Health, RePORTER application 10358797, Role of semaphorin signaling in neuronal recovery from dendritic injury: a comparative case study in-vitro and in-vivo (1R15NS125565-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10358797. Licensed CC0.

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