# Uncovering single-cell transcriptional dynamics in somitogenesis in live zebrafish embryos

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $441,375

## Abstract

Project Summary/Abstract
In vertebrate development, somites—morphological segments that prefigure the bones and muscles of the
adult—are formed rhythmically and sequentially at the posterior end of the elongating body axis of the embryo.
This rhythmic specification is dictated by a highly conserved biological clock that consists of an oscillatory gene
regulatory network. In humans, failure of this network to robustly oscillate in individual cells or to synchronize
tissue-wide oscillations across neighboring cells has been associated with developmental defects such as
scoliosis.
Despite years of research identifying the molecular components of this oscillatory network, we still do not
understand the mechanisms affected by important disease-causing mutations in these components. Crucially,
to date, the vast majority of information about this highly dynamic developmental process stems from
inferences from fixed tissue or from fluorescent reporters whose maturation time is too slow to reveal the
mechanistic basis of these mutations at the level of their transcriptional dynamics.
To overcome this major obstacle, we established the MS2 system to measure the dynamics of transcriptional
initiation of genes within this network in individual cells of living, developing zebrafish embryos, a widespread
model of somitogenesis and scoliosis. This new ability empowers us to revisit the molecular processes
underlying vertebrate segmentation from the standpoint of the dynamics of individual cells. Using this
technology, we have discovered that the smooth protein oscillations that characterize somitogenesis are
produced by bursts of transcriptional initiation. Here, we propose to characterize zebrafish somitogenesis in
healthy conditions and to uncover (i) the molecular origins of transcriptional bursting in somitogenesis and (ii)
how these bursts are coordinated between neighboring cells through signaling pathways in order to produce
the coherent tissue-wide oscillations necessary for healthy development. We envision that our work will set the
stage for precisely diagnosing the molecular underpinnings of disease phenotypes in vertebrate development.
Further, the experimental and computational technologies developed here will empower the biology community
to launch explorations into the single-cell nature of vertebrate development dynamics on par with what is
currently attainable in invertebrate animals. Ultimately, this knowledge—combined with the innovated
technologies and analyses proposed here—will make it possible to rationally modify these transcriptional
dynamics at will for bioengineering or therapeutic purposes.

## Key facts

- **NIH application ID:** 10742431
- **Project number:** 1R21HD107436-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Hernan Gustavo Garcia
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $441,375
- **Award type:** 1
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10742431

## Citation

> US National Institutes of Health, RePORTER application 10742431, Uncovering single-cell transcriptional dynamics in somitogenesis in live zebrafish embryos (1R21HD107436-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10742431. Licensed CC0.

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