# Mechanisms of specification, quiescence, and regeneration of primordial germ cells

> **NIH NIH R35** · BROWN UNIVERSITY · 2022 · $572,546

## Abstract

Project Summary
 Sexual reproduction requires a germline, a lineage of cells formed in early embryos that ultimately
develops into eggs or sperm in the adult. Lore has it that when you lose your germline in development, you
become a sterile adult. In many animals, especially in the current favorites of lab animals, that is largely true.
 We use “rule breakers” though and find such lore unfounded. Our work focuses on the biology of primordial
germ cells, how they form during early development, and how they regenerate when the originals are removed.
Our work leverages embryos from a sister group to chordates – the sea star and sea urchin. While not
common organisms for biomedical research, these echinoderms have many strategic benefits for revealing
unique perspectives in the biology of germline formation and regeneration. Millions of synchronous embryos
from a single male/female cross allow biochemical and metabolic analysis of the germline, the resultant
embryos have ideal transparency for in vivo longitudinal imaging, they develop rapidly, are easy to manipulate
(single cell drop-mRNA-seq, optogenetics, cell and tissue transplantations) and they are well suited to
complementary gene perturbation approaches (CRISPR/Cas9, morpholinoantisense oligonucleotides, MASO),
and small molecule perturbations. The existing deep genomic and reagent resources for these animals,
coupled with their tractable experimental characteristics, yields a unique system for understanding primordial
germ cell biology with defined molecular and morphological endpoints, in live embryos with longitudinal
analysis, distinct metrics of quantitation, and transgenerational evaluations.
 We interrogate all levels of gene expression for this work, from chromatin modification to post-
transcriptional processing and post-translational networks, because that is what the embryos are “telling” us is
needed to understand these complex, and deeply rooted events in sexual reproduction. Our work emphasizes
longitudinal, in vivo analysis using high resolution optical imaging coupled with genomic perturbations, signal
pathway manipulations and manual transplantations and expirations to leverage contrasting mechanisms in
germ cell formation between closely related organisms. Sea urchins and sea stars have historically not been
genetically manipulated, and this reason is precisely how germ line regeneration has been discovered in this
and other animals seen to bear this trait. Relying on manual manipulations meant the genes needed for
regeneration were not disturbed, revealing their germ cell regenerative abilities. With new state-of-the-art
technologies, these animals can now be exploited with transgenerational analysis. Overall, our work
interrogates important biological questions from unique experimental perspectives using rule-breaking models
for innovation in the pursuit of new knowledge.

## Key facts

- **NIH application ID:** 10414946
- **Project number:** 5R35GM140897-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** GARY M WESSEL
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $572,546
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414946

## Citation

> US National Institutes of Health, RePORTER application 10414946, Mechanisms of specification, quiescence, and regeneration of primordial germ cells (5R35GM140897-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10414946. Licensed CC0.

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