# Functional contribution of Metabolism in embryonic development

> **NIH NIH R21** · BROWN UNIVERSITY · 2022 · $199,375

## Abstract

PROJECT SUMMARY
Aerobic glycolysis was first identified in cancer cells (Warburg effect). This unusual metabolic process is
considered to supply necessary biosynthetic products to sustain DNA, protein, and membrane synthesis
in highly proliferative cells. However, the actual physiological significance of glycolysis remains largely
unknown. Recent reports suggest that aerobic glycolysis may directly influence cellular function and
development beyond matching a cell’s biosynthetic demands. Indeed, in our preliminary metabolomics
results using the sea urchin embryo as a model system, dynamic metabolic regulation appears to be
present throughout embryogenesis and further critical for a specific cell signaling event that occurs at the
16-cell stage of the embryo (5 hours post fertilization; 5hpf). This signaling event is called “micromere
signaling” and known to drive endomesodermal specification in the entire embryo at two days post
fertilization (2dpf). Based on these preliminary findings, we hypothesize that dynamic metabolic
regulation serves as another layer of mechanism for cell specification and signaling during
embryogenesis. To prove this hypothesis, in the proposed research, we will first visualize metabolic
dynamics in real time and in vivo throughout embryogenesis, using GFP-tagged metabolic sensors.
Imaging will be performed by 4D-confocal microscopy to maximize the spatial and temporal
resolution of metabolic dynamics, which will be further subject to quantitative analysis for each cell
lineage and for each developmental stage. Second, we will test the functional significance of each
metabolic pathway (Glycolysis, Fatty Acid Synthesis, Oxidative Phosphorylation), especially in the
event of micromere signaling at the 16-cell stage. Multiple inhibitors for each metabolic pathway will
be applied for ~0.5 hour to the entire embryo or specifically to the micromeres at the 16-cell stage.
The latter will be accomplished by constructing chimeric embryos in which the micromeres are
replaced with the inhibitor-treated micromeres. The phenotypes will be then scored by analyzing
temporal and spatial expression of polarity factors and fate determinants that drive the micromere-
specific Gene Regulatory Network and is critical for endomesodermal specification, as well as
overall morphology (e.g. successful gastrulation) in the resultant embryos. These experiments will
identify the essentiality of each metabolic pathway to entire embryonic patterning. Overall, the
proposed research will reveal the functional interplay of metabolic, gene and protein regulations essential
for embryonic development, which is still understudied in the field of cell and developmental biology.

## Key facts

- **NIH application ID:** 10497320
- **Project number:** 1R21HD109132-01
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Mamiko Yajima
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $199,375
- **Award type:** 1
- **Project period:** 2022-09-12 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10497320

## Citation

> US National Institutes of Health, RePORTER application 10497320, Functional contribution of Metabolism in embryonic development (1R21HD109132-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10497320. Licensed CC0.

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