# Germ cell specification and differentiation in planarians

> **NIH NIH R01** · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · 2021 · $266,730

## Abstract

Project Summary/Abstract
Germ cells give rise to gametes–oocytes and sperm–that fuse to create a totipotent zygote, which divides and
generates all the cells of an organism. During development, a new germ cell lineage must be established and
differentiate properly to ensure propagation of the species. Most knowledge of germ cell specification and
development comes from model organisms in which maternal determinants specify germ cells early in
embryogenesis. By contrast, many animals (including mammals) specify their germ cells in response to
inductive cues from surrounding cells later in development. Despite these differences in germline
establishment, all germ cells share several important features, such as intrinsic transcriptional repression of
somatic cell programs and dependence on extrinsic factors from somatic support cells. The free-living
planarian flatworm, Schmidtea mediterranea, is well known for its extraordinary regenerative prowess, which
relies on a population of pluripotent somatic stem cells. Planarians specify their germ cells post-embryonically
from these somatic stem cells in response to inductive cues. Strikingly, planarians can even regenerate new
germ cells de novo. Work over the past decade has established the planarian as a tractable model in which to
study germ cell biology, and several intrinsic and extrinsic factors that regulate distinct aspects of male
germline development–specification, maintenance, and differentiation–have been identified. However, almost
nothing is known about female germ cell development in these animals, a critical gap because of the important
role of egg production in the pathology of parasitic flatworm diseases. Here, building on extensive preliminary
data from the applicant’s laboratory, the following two aims are proposed: (i) to functionally characterize the
ovarian transcriptome; and (ii) to examine the role(s) of monoamine neurotransmitters in germ cell
development. In Aim 1, laser capture microdissection and next-generation RNA sequencing will be used to
create ovary- and testis-enriched transcriptomes. Validating ovary-enriched expression by in situ hybridization
and characterizing gene function by RNA interference will enable the identification of germ cell-intrinsic and
extrinsic regulators of female germ cell development. In Aim 2, cutting-edge mass spectrometry-based
metabolomic studies will be combined with gene expression mapping and functional approaches to investigate
the biogenic monoamines that signal locally and/or systemically to regulate germ cell development. The
proposed experiments capitalize upon the planarian’s regenerative abilities and the functional genomic tools
available for studying these animals to acquire a comprehensive view of the genes regulating female germ cell
development. These studies are significant as they are expected to enhance understanding of germ cell
biology across the metazoans and help guide future experiments on mammalian systems. In additio...

## Key facts

- **NIH application ID:** 10169480
- **Project number:** 5R01HD043403-17
- **Recipient organization:** MORGRIDGE INSTITUTE FOR RESEARCH, INC.
- **Principal Investigator:** Phillip A Newmark
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $266,730
- **Award type:** 5
- **Project period:** 2003-01-09 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169480

## Citation

> US National Institutes of Health, RePORTER application 10169480, Germ cell specification and differentiation in planarians (5R01HD043403-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10169480. Licensed CC0.

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