# Systems analysis of mouse gastrulation

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $330,400

## Abstract

Project Summary
 Gastrulation is the fundamental event during embryogenesis that generates the three primary germ
layers from the pluripotent epiblast. To understand this intricate process, it is essential to use systems-based
approaches to elucidate the genetic regulatory network that controls the tightly coordinated events of
patterning, differentiation, and morphogenesis that take place during gastrulation. In this application, we will
use sophisticated computational tools for the de novo reconstruction of regulatory networks to investigate
mouse gastrulation. In our preliminary studies, we have generated a genetic regulatory network (interactome)
for mouse epiblast stem cells (EpiSC) using unbiased reverse-engineering approaches. Using gene expression
signatures generated from peri-gastrulation mouse embryos, we have interrogated the EpiSC interactome to
identify candidate master regulators of gastrulation, as well as cis-regulatory sequence motifs and cognate
transcription factors that are likely to be active during gastrulation. Therefore, based on these preliminary
findings, we hypothesize that our systems approach can identify novel master regulators of key biological
processes during mouse gastrulation.
 We will now pursue a comprehensive analysis of the genetic regulatory network that governs mouse
gastrulation through three linked specific aims: (1) Identification of master regulators of mouse epiblast during
gastrulation by unbiased systems analyses using signatures from peri-gastrulation mouse embryos to
interrogate the EpiSC interactome for the identification of candidate master regulators, followed by functional
validation studies; (2) Analysis of the transcriptional network that regulates mouse gastrulation by
computational identification and experimental validation of cis-regulatory motifs and cognate transcription
factors that are likely to function in gastrulation; and (3) Functional analyses of the regulatory network for
gastrulation by testing the inferred regulatory network and biological functions of master regulators using
signatures from mouse mutants that are defective in gastrulation, and by performing loss-of-function analyses
of candidate master regulators in mouse embryos in vivo. Taken together, these studies will provide novel
mechanistic insights into a central biological process that is essential for proper embryonic development, and
whose perturbation can lead to major congenital defects.

## Key facts

- **NIH application ID:** 9906071
- **Project number:** 5R01HD085904-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** MICHAEL M. SHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $330,400
- **Award type:** 5
- **Project period:** 2016-07-10 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906071

## Citation

> US National Institutes of Health, RePORTER application 9906071, Systems analysis of mouse gastrulation (5R01HD085904-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9906071. Licensed CC0.

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