# Regional specific metabolism regulates specification of the Spemann Organizer

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $703,249

## Abstract

Project Summary
Congenital heart disease is a major cause of illness in newborns and children. While studying Leigh’s
syndrome, a mitochondrial metabolism disease caused by LRPPRC that also causes congenital heart disease
and heterotaxy, we were surprised to discover that regional metabolism in the early Xenopus embryo dictates
cell fate. We found that the Spemann-Mangold Organizer (the Organizer) depends on regional metabolism. In
fact, our work demonstrates that Hif-1α regulates the specification of the Organizer and that the Organizer
consumes 20% more oxygen than more ventral (non-Organizer) tissue. To reconcile an increase in oxygen
consumption and activation of Hif-1α, we discovered that the Organizer has “leak” metabolism, which we have
proposed previously in our group to be caused by the c-subunit of the ATP Synthase. This proposal
investigates a signaling pathway that connects canonical Wnt signaling, Hif-1α, and regional metabolism to
understand an iconic signaling center, the Spemann-Mangold Organizer.

## Key facts

- **NIH application ID:** 10825929
- **Project number:** 1R01HD114493-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Elizabeth Ann Jonas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $703,249
- **Award type:** 1
- **Project period:** 2024-07-10 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825929

## Citation

> US National Institutes of Health, RePORTER application 10825929, Regional specific metabolism regulates specification of the Spemann Organizer (1R01HD114493-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10825929. Licensed CC0.

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