# Determining Mechanisms of Regenerative Neural Specification

> **NIH NIH R01** · LEHIGH UNIVERSITY · 2021 · $321,908

## Abstract

Project Summary:
To date the mechanisms that specify individual neuronal fates during regeneration are poorly understood.
Determining how regenerative specification programs promote successful regeneration is an essential step to
improve the design of regenerative therapies. However, to date we lack sufficient examples of regenerative
neuronal patterning, which hampers our ability to better determine how the proper neuronal fates are
generated during regeneration. We do know that regeneration doesn't recapitulate developmental patterning,
which suggests that changes to fate known specification programs are necessary for regenerative
neurogenesis. Because regeneration doesn't recapitulate development, being able to compare how changes to
the developmental patterning programs result in regenerative success will provide key insights that will improve
our understanding of how to promote regeneration. Thus, there is a critical need to identify regenerative
neuronal patterning mechanisms in animals suited for comparing the developmental and regenerative
programs that generate identical cell types. The PI's long-term goal is to understand how regenerative specific
patterning programs promote successful regeneration. To advance this goal the PI developed the highly
regenerative and excellent developmental system the sea anemone Nematostella vectensis as a model to
investigate developmental and regenerative neurogenesis. The PI has identified a neurogenic transcription
factor (NvashA) that is differentially deployed during regeneration and development, indicating that its
regenerative function is different than its developmental role. Similarly, we also identified a class of neurons
described by the NvLWamide::mcherry reporter. During development these neurons require NvashA for proper
specification. Three of the five subtypes of NvLWamide neurons show differences between their
developmental and regenerative formation. This work will use a series of conditional alleles and in vivo imaging
to functionally determine if some of the regeneration specific differences in NvLWamide fate specification are
explained by changes in their requirement for NvashA. To determine how NvashA functions during
regeneration the regenerative targets of NvashA will be identified using an RNAseq approach. Lastly, to gain
insights about how new NvLWamide neurons are patterned during regeneration, and to gain insights about
how remnant neurons reintegrate during neuronal regeneration the transcriptomes of regenerating NvLWamide
neurons will be determined at multiple time points throughout regeneration, and NvLWamide genes that
change over time will be mapped to newly forming or remnant neurons. This work will demonstrate that
developmental patterning genes play distinct roles during regeneration, and that neuronal cell types require
new specification programs to regenerate. The foundation of data generated in this proposal will allow the PI to
make a sustained impact in the field ...

## Key facts

- **NIH application ID:** 10093083
- **Project number:** 5R01GM127615-03
- **Recipient organization:** LEHIGH UNIVERSITY
- **Principal Investigator:** Michael John Layden
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $321,908
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10093083

## Citation

> US National Institutes of Health, RePORTER application 10093083, Determining Mechanisms of Regenerative Neural Specification (5R01GM127615-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10093083. Licensed CC0.

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