# Neuronal guidance landscape across development and regeneration

> **NIH NIH P20** · DARTMOUTH COLLEGE · 2024 · $238,197

## Abstract

Functional neural circuits require accurate wiring by axons. Axonal targeting is mediated by a unique repertoire 
of guidance receptors differentially expressed on the axons of given neuronal populations. These receptors 
recognize spatially distributed guidance cues across an axon’s trajectory to guide directional axonal growth and 
ultimately the formation of appropriate synaptic connections. This complex cell to cell signaling is dynamic, 
spatially-regulated, and differs between neuronal populations and their targets. In a nervous system vulnerable 
to injury, regeneration of damaged motor axons back to their original muscle targets is essential for recovery of 
coordinated movement. Growing evidence demonstrates that axon regeneration is not simply a recapitulation of 
development, but that it requires unknown injury-dependent cues. Yet, what are the guidance receptors and cues 
that mediate topographically correct axon targeting and what is their spatial distribution? How does the cell 
signaling underlying circuit formation differ between developing and regenerating tissues? Understanding the 
cellular and molecular mechanisms that mediate regenerative axon guidance represents an important 
and unaddressed goal that is relevant to recovery from injury or disease. To fill the existing knowledge gaps, I developed a unique model using the motor innervation of the larval 
zebrafish pectoral fin, which is homologous to tetrapod forelimbs. Importantly, this model allows for the in vivo 
observation of individual axons and their synaptic targets from development through regeneration. Monitoring 
distinct sub-populations of motor neurons reveals that they innervate topographically defined domains in the fin 
musculature. To find their targets, motor neuron axons must first navigate to the fin, sort between the abductor 
and adductor muscles, and grow to their appropriate muscle domain where they will form functional synapses. I 
have previously demonstrated that after laser-mediated axon transection, individual regenerating motor axons 
precisely return to their originally-specified muscle and target domains in the fin via unknown mechanisms. The 
long-term goal of my research program is to determine the molecular and cellular signaling that enables neuronal 
populations to re-establish such precise targeting. Given that each of the stepwise choice points along an axon’s 
route requires distinct guidance signaling mechanisms, a candidate-based approach to test the role of individual 
guidance cues is not efficient and will not provide a comprehensive understanding of the complex landscape 
through which an axon is guided. Thus, a critical foundation to support my research is the generation of a 
spatially-resolved single cell transcriptome of the motor neuron sub-populations as well as the cells of the fin that 
they target. The Center for Quantitative Biology (CQB) COBRE will advance my research career goals by 
providing me with the necessary sc...

## Key facts

- **NIH application ID:** 11141398
- **Project number:** 2P20GM130454-06
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Lauren J Walker
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $238,197
- **Award type:** 2
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11141398

## Citation

> US National Institutes of Health, RePORTER application 11141398, Neuronal guidance landscape across development and regeneration (2P20GM130454-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11141398. Licensed CC0.

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