# Identifying genetic pathways and cellular sources for neural regeneration in adult animals

> **NIH NIH F31** · HARVARD UNIVERSITY · 2020 · $31,502

## Abstract

Project Summary/Abstract
Adult animals capable of whole-body regeneration are tasked with faithfully replacing any missing cell type,
including the myriad of cell types within the nervous system. Most knowledge regarding the patterning and
specification of neuronal populations comes from work focusing on embryonic development; however, limited
work has been performed to identify mechanisms underlying the regeneration or re-specification of entire
nervous systems within adult animals. The overall objective of this project is to uncover the cellular and
molecular mechanisms that underlie neuronal cell specification, differentiation, and replacement within the
context of an adult animal, using the highly regenerative acoel research model, Hofstenia miamia. Hofstenia
has an organized nervous system composed of different neural cell types that it can regenerate fully because
of a population of pluripotent adult stem cells called ‘neoblasts’. Notably, Hofstenia is amenable to mechanistic
studies of regeneration and presents several advantages over more well-established invertebrate regeneration
models, including accessible embryos that have enabled CRISPR/Cas9-based genome editing and stable
transgenesis. This project will ask two major questions about nervous system regeneration within the adult
nervous system: 1) What are the molecular/genetic regulators of neural cell type diversity during regeneration?
2) What are the cellular sources and dynamics that underlie differentiation of neural populations during
regeneration? Single-cell RNAseq will identify candidate regulators of neural cell type diversity, focusing on
transcription factors and receptors, during regeneration. Our preliminary scRNAseq data allows us to
hypothesize sox4, vax1, and nkx2.4 homologs as important regulators of neural differentiation. Systemic RNAi
in combination with microscopy in adults will identify the molecular mechanisms governing neural cell type
identity during regeneration. In parallel, we plan to utilize a transgenic labeling technique to identify neural stem
cell populations, determining their dynamics and contributions to differentiated neural populations during
regeneration. These two questions allow us to test the hypothesis that a single neural stem cell population
subfunctionalizes to form progenitor subtypes within Hofstenia. Cell and molecular mechanisms discovered in
the regeneration of the adult nervous system in this work have the potential to inform human regenerative
medicine with regards to neurodegenerative disease. My goal for the F31 is to equip myself with the
computational, genetic, and theoretical skills necessary for a lifetime career in developmental biology to
uncover the intricacies associated with animal regeneration. The Department of Organismic and Evolutionary
Biology at Harvard University is a premier institution for this training.

## Key facts

- **NIH application ID:** 9992764
- **Project number:** 1F31GM134633-01A1
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Ryan Edward Hulett
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,502
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992764

## Citation

> US National Institutes of Health, RePORTER application 9992764, Identifying genetic pathways and cellular sources for neural regeneration in adult animals (1F31GM134633-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9992764. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*