# Molecular mechanisms of the maternal to zygotic transition

> **NIH NIH R35** · YALE UNIVERSITY · 2021 · $800,073

## Abstract

SUMMARY
The maternal to zygotic transition is a universal step in animal development, where the embryo
transitions from a maternally driven program to a zygotic program. This requires the clearance of the
maternally provided mRNAs, and transcription of the zygotic genes. Indeed, these two processes are
intimately interconnected, 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 identified individual factors regulating mRNA stability and activation of the
zygotic genome, we lack major understanding on 1) how different regulatory mechanisms are
integrated to instruct mRNA turn over and translation regulation in the embryo, 2) what are the
mechanisms that regulate protein output and genome activation, and 3) what is the regulatory code
(sequences, structures and RNA modifications) that shape genome activation and post-trasncriptional
regulation. By combining high throughput sequencing, protein-RNA interaction maps, with novel
methods to assay the regulatory activity of the transcriptome in the early embryo, we will define the
factors that are recruited to the genome to activate the zygotic program, the mechanisms that activate
the chromatin, the sequence/structural motifs (code) that determine maternal mRNA fate, the readers
that interpret the code and the mechanisms that trigger each of these steps in vivo. Together these
proposed experiments, will define the gene regulatory network that controls early vertebrate
development.
The proposed project is relevant for public health at different levels. First, from the stand point of human
disease and cancer, pathways that control mRNA stability (including miRNAs) play an important role in
aberrant oncogene activation in cancer, and are relevant to changes in cell fate where the cells need to
install a new program and remove the previous cellular program through post-transcriptional regulation.
Second, from the stand point 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 of 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 derived from this project will help us understand how gene expression is regulated in the
early embryo during the maternal to zygotic transition to ultimately trigger the activation of the different
developmental pathways during embryogenesis.

## Key facts

- **NIH application ID:** 10136627
- **Project number:** 5R35GM122580-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Antonio J Giraldez
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $800,073
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-08-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136627

## Citation

> US National Institutes of Health, RePORTER application 10136627, Molecular mechanisms of the maternal to zygotic transition (5R35GM122580-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10136627. Licensed CC0.

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