# The gut endoderm: origin, formation and fate

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2021 · $648,756

## Abstract

PROJECT SUMMARY / ABSTRACT
The gut endoderm is the precursor tissue of the respiratory and digestive tracts, and their associated visceral
organs. In this project we will use a suite of state-of-the-art technologies to address fundamental questions
focused on mechanisms of mammalian gut endoderm cell lineage commitment and tissue morphogenesis, as
well as probing the developmental origin and fate of cells that comprise the gut endoderm, using the mouse
model.
Our previous studies have provided a paradigm-shift in our understanding of the origin and mechanism of
formation of the gut endoderm. Using fate mapping, live imaging and more recently single-cell transcriptomic
methods, we demonstrated that the gut endoderm of mice comprises cells of two distinct developmental
origins; embryonic definitive endoderm, and extra-embryonic visceral endoderm. The dual origin of the gut
endoderm challenges the prevailing view of germ layer formation in mammals which posits that endoderm,
along with mesoderm and ectoderm, derives solely from pluripotent epiblast. We have also shown that the gut
endoderm forms through a novel intercalation mechanism and identified SOX17 as a critical regulator of
this process.
The broad aim of this project is to use molecular, genomic, embryological and imaging techniques to
investigate fundamental open questions pertaining the origin, formation and fate of the gut endoderm in
mammals. Specific Aim 1 will investigate the dynamic cellular behaviors driving gut endoderm
morphogenesis. Specific Aim 2 will probe the mechanism(s) by which the SOX17 transcription factor drives
gut endoderm cell fate specification, tissue morphogenesis and communication between embryonic definitive
endoderm and extra-embryonic visceral endoderm cells as they form a congruent epithelium. Specific Aim 3
will determine whether descendants of extra-embryonic visceral endoderm cells persist throughout embryonic
development and whether they will ultimately contribute to the endodermal organs of the adult.
A rigorous understanding of the normal gut endoderm, encompassing its origin, formation and fate, will
underpin logical efforts to direct the differentiation of cells into endoderm identities, generate bona fide
endodermal organoids for development and disease modeling and screening, understand disease progression
and design new therapeutic strategies for these vital organ systems when they fail.

## Key facts

- **NIH application ID:** 10156809
- **Project number:** 1R01DK127821-01
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** ANNA-KATERINA HADJANTONAKIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $648,756
- **Award type:** 1
- **Project period:** 2021-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10156809

## Citation

> US National Institutes of Health, RePORTER application 10156809, The gut endoderm: origin, formation and fate (1R01DK127821-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10156809. Licensed CC0.

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