# Decoding neural cell fate diversity

> **NIH NIH R21** · UNIVERSITY OF OREGON · 2021 · $405,625

## Abstract

PROJECT SUMMARY/ABSTRACT
Cell fate diversification is a critical step in producing the many neuronal subtypes required for
functional circuitry in the vertebrate brain. We know a considerable amount about how neural
progenitors diversify fates to form distinct daughter neurons. However, much less is known
about later processes that diversity the fates of postmitotic neurons. One reason for this
knowledge gap is that in most vertebrate models it is impossible to recognize and study
precisely the same neurons in separate individuals, limiting predictive and statistical power. We
can overcome these limitations in zebrafish by studying two adjacent, individually identifiable,
spinal motoneurons. We discovered that these neurons are initially equivalent, and that
interactions between them, in addition to interactions with an identified set of muscle fibers,
breaks the equivalence between the two neurons and causes them to adopt distinct fates.
Moreover, one of these neurons then typically dies, an important fate for sculpting brain
architecture and circuitry. This is a unique situation in vertebrates, in which we can observe fate
diversification as it is occurring in living embryos and predict that a neuron will die well before
the process occurs, yet we still do not know the underlying molecular events. We will overcome
this barrier using a variety of tools that enable us to manipulate the fates of these two neurons
and single cell RNA sequencing at defined stages during the developmental process. This
combination with enable us to discover genes involved in neuronal cell fate diversification as
well as genes that predict neuronal cell death and survival. We plan to validate these genes
using quantitative RNA in situ hybridization techniques. We will then test validated candidates
using an innovative F0 CRISPR screen. Our proposed studies will reveal genes previously
unknown to function during neuronal cell fate diversification, survival, and death. If successful,
they will uncover genetic mechanisms of neuronal cell fate diversification with unprecedented
precision, and thus will open new avenues of inquiry and deepen our understanding of
neurodevelopmental mechanisms.

## Key facts

- **NIH application ID:** 10283597
- **Project number:** 1R21NS123803-01
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** JUDITH S EISEN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $405,625
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10283597

## Citation

> US National Institutes of Health, RePORTER application 10283597, Decoding neural cell fate diversity (1R21NS123803-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10283597. Licensed CC0.

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