# Intrinsic Pathways Regulating Sensory Axon Regeneration in Zebrafish Larvae

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $31,562

## Abstract

Project Abstract:
Axon damage after stroke, traumatic injury or disease disrupts neuronal circuits and can result in disability.
Mammalian central axons do not regenerate well, but peripheral axons have a greater, if limited, potential to
regrow. Axon regeneration is influenced by extrinsic and intrinsic factors; the intrinsic mechanisms regulating
axon regeneration in vertebrates are not well understood. Because the environments of both the central and
peripheral nervous systems are permissive for axon regeneration in fish, I can use them to study the role of
intrinsic pathways in this process. Dual Leucine Kinase (DLK) is a mitogen-activated protein kinase kinase
kinase (MAP3K) that initiates a signaling cascade upon axon damage that promotes axon regeneration.
Although DLK is known to be a critical regulator of axon regeneration in worms, flies, and mice, its interactions
with other MAPK pathways are still not well understood, the downstream processes it activates are not fully
understood, and it is unclear if these pathways are necessary for regeneration of all types of neurites.
Vertebrates have two similar DLK-related MAP3K proteins, DLK and LZK (Leucine kinase zipper). Vertebrate
DLK shares more sequence identity with worm DLK-1, but only LZK shares a calcium-sensing domain at the c-
terminus with DLK-1. While DLK gene trap mutants in mice have significantly slower axon regeneration,
regeneration is not prevented altogether, suggesting that LZK may also contribute to axon regeneration (Chen
et al, 2016). Although DLK is required for axon regeneration in fly sensory neurons, it is not required for
regeneration of their dendrites. Unlike these bipolar Drosophila sensory neurons, somatosensory neurons are
unipolar: they have central and peripheral axons, but no dendrites. I established a zebrafish model to study the
function of DLK and LZK signaling in somatosensory neuron repair. With this model I will clarify several
important questions about these signaling pathways: 1) Are both DLK and LZK required the regeneration of
peripheral and central sensory axons? Are their functions redundant or complimentary? 2) What are the
specific MAP2Ks and MAPKs involved in this process? 3) Do DLK and LZK regulate physiological changes
associated with axon regeneration? Zebrafish larvae provide an amenable model for addressing these
questions in live animals, with single cell resolution.

## Key facts

- **NIH application ID:** 9998042
- **Project number:** 5F31NS106742-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** KADIDIA PEMBA ADULA
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,562
- **Award type:** 5
- **Project period:** 2018-09-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998042

## Citation

> US National Institutes of Health, RePORTER application 9998042, Intrinsic Pathways Regulating Sensory Axon Regeneration in Zebrafish Larvae (5F31NS106742-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9998042. Licensed CC0.

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