# Molecular mechanisms of the maternal to zygotic transition

> **NIH NIH R35** · YALE UNIVERSITY · 2023 · $825,334

## Abstract

SUMMARY
The maternal to zygotic transition is a universal step in animal development characterized by the
clearance of the maternally provided mRNAs and the activation of the zygotic genome. Indeed, these
two processes are intimately interconnected as maternal factors drive the activation of the zygotic
genes, and zygotic products actively target maternal mRNAs for deadenylation, repression and
clearance.
While recent studies have began identifying individual factors regulating mRNA stability and activation
of the zygotic genome, we lack major understanding on 1) the regulatory code (sequences, structures
and readers) that shapes genome activation and post-transcriptional regulation, 2) the mechanisms that
regulate protein output and genome activation, and 3) how different regulatory mechanisms are
integrated to instruct mRNA turnover, translation regulation and genome activation in the embryo. We
will combine massive parallel reporter assays to determine the regulatory activity of different sequences
in the early embryo, protein interaction maps (at the level of the DNA and RNA) to define the factors
that mediate transcriptional and post-transcriptional regulation and novel imaging approaches to
determine how pioneer factors shape chromatin structure and in turn genome activation. Together
these experiments will define the mechanisms that trigger each of these steps in vivo and the gene
regulatory network that controls early vertebrate development.
This project is relevant for public health at different levels. First, from the standpoint of human disease
and cancer, pathways that control mRNA stability play an important role in aberrant oncogene
activation in cancer and are relevant to changes in cell fate where the cells need to transition to a new
program and remove the previous one through post-transcriptional regulation. Second, from the
standpoint of reproductive health, infertility is estimated to affect 15% of reproductive age women and
early pregnancy loss corresponds to 25% of all pregnancies with up to 70% in pregnancies after in vitro
fertilization. Understanding the mechanisms of zygotic genome activation and maternal mRNA decay
can provide fundamental insights in human infertility and tools to evaluate early loss of fertilized eggs.
The results we derived here will help us understand how gene expression is regulated in the early
embryo to trigger the activation of different developmental pathways during embryogenesis.

## Key facts

- **NIH application ID:** 10685563
- **Project number:** 5R35GM122580-07
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Antonio J Giraldez
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $825,334
- **Award type:** 5
- **Project period:** 2017-05-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10685563

## Citation

> US National Institutes of Health, RePORTER application 10685563, Molecular mechanisms of the maternal to zygotic transition (5R35GM122580-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10685563. Licensed CC0.

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