# Molecular and Cell Biology of Neuromesodermal Progenitors

> **NIH NIH R35** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $159,607

## Abstract

Abstract (taken from the parent grant)
We aim to understand the normal biology of neuromesodermal progenitors (NMPs), as well as to use NMPs to
model cellular and molecular mechanisms in vivo. NMPs are basal progenitor cells located in the tailbud of
vertebrate embryos that continue to make a germ-layer decision after gastrulation to generate ectoderm and
mesoderm. As a primary source of cells generating the spinal cord, skeletal muscle, and other mesodermal
derivatives, NMPs are a key cell type contributing to the formation of the vertebrate body plan. Studying NMPs
has advanced our understanding of how body plans are generated, improved techniques for in vitro tissue
generation, and provided critical insights into signaling pathway mechanisms. I discovered zebrafish NMPs as
a postdoctoral fellow and my lab continues to focus on them. Our recent work has uncovered important roles
for the transcription factor Sox2 in maintaining NMPs in an undifferentiated state through interactions with the
canonical Wnt signaling pathway. This, combined with the past research showing the Wnt signaling effector
bcat physically interacts with Sox2, indicates Wnt signaling can modulate gene expression and biological
activity directly via Sox2. Little is known about this exciting branch of the Wnt/ bcat pathway. We will interrogate
this pathway of Sox2 and Wnt/ bcat interactions at a number of biological levels, focusing on direct physical
interactions between Sox2 and bcat, as well as genome wide analysis of Sox2/ bcat mediated transcriptional
regulation. We hypothesize that Sox2/ bcat signaling represents a new arm of the Wnt/ bcat pathway distinct
from the canonical TCF/LEF transcription factor family mediated signaling. We also recently developed a new
Cyclin Dependent Kinase biosensor transgenic zebrafish and observed that NMPs and some of their
derivatives exist in restricted cell cycle phases. The NMPs are held primarily in the G2 phase, while
mesodermal notochord progenitors are restricted to the G1 phase. Cell cycle phase is broadly implicated in
various aspects of stem cell maintenance, cell differentiation, and cell migration and invasion. We will
manipulate the cell cycle in NMPs and their derivatives to understand how the cell cycle phase impacts normal
NMP development. We hypothesize that the G2 phase restriction of NMPs is essential for maintenance of the
undifferentiated state and for receipt of Wnt signaling based on G2 dependent receptor activation. We also
hypothesize that the G1 phase of notochord progenitors is essential for their morphogenetic behavior of
convergence and extension. Together, our work will shed important light on not only NMP development and
vertebrate body plan formation, but also basic principles of cell biology and signaling. Wnt/ bcat signaling and
Sox2 are found together and play important roles in numerous normal and diseased cellular contexts, including
stem cells and cancer. The cell cycle is a fundamental aspect of nor...

## Key facts

- **NIH application ID:** 11098153
- **Project number:** 3R35GM150290-02S1
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Benjamin L Martin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $159,607
- **Award type:** 3
- **Project period:** 2023-06-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11098153

## Citation

> US National Institutes of Health, RePORTER application 11098153, Molecular and Cell Biology of Neuromesodermal Progenitors (3R35GM150290-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11098153. Licensed CC0.

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