Completed Genetics & Molecular Biology Cells, Biochemistry & Physiology

Patterning embryos with genetic oscillations.

Funder Wellcome Charity-funded
Recipient organisation University College London
Funding £2.2M
Period Oct 2012 — Mar 2018

In plain English

AI plain-English summary

A zebrafish embryo’s backbone forms not all at once, but segment by segment, driven by a genetic clock that ticks in its cells. This project investigates the “segmentation clock”—a set of genes that turn on and off in rhythmic waves, telling cells where to build vertebrae. When this clock breaks, babies can be born with fused or missing vertebrae. Scientists know the clock exists, but they do not understand how individual cells keep time, how they synchronise with neighbours, or what stops the clock once the backbone is complete. The researcher will watch the clock tick in real time using specially engineered zebrafish whose cells glow each time a clock gene activates. If successful, this work will reveal the fundamental rules of how genetic oscillators build body patterns. That knowledge could eventually help explain why some human embryos develop spinal defects, and might guide efforts to grow replacement vertebrae or repair spinal injuries. But this is primarily fundamental science—it asks how a living system assembles itself with precision, a question that has no immediate practical payoff but whose answer could reshape developmental biology.

View original technical description
I will investigate the regulation and dynamics of the segmentation clock using a set of novel zebrafish transgenic lines that allow the direct visualization of genetic oscillations in real time in the developing embryo. Aim 1 focuses on the mechanism of single cell oscillations arising from a transcriptional negative feedback loop of the Her genes. We will measure the dynamic properties of cultured clock cells from her mutant backgrounds, study in vivo binding sites of Her proteins using Chi p-seq, dissect regulatory regions of her gene promoters, and measure stability of Her proteins. Aim 2 studies the interaction of cells in culture by time-lapse imaging as they make defined cell-cell contact on patterned substrates and adjust their oscillations in response to Delta/Notch signaling. Aim 3 examines how oscillators are slowed and stopped by measuring the rate of slowing across the presomitic mesoderm in time-lapse recordings with different FGF and Wnt gradient perturbations, and comparing this to the effect of these factors on isolated oscillating cells. The role of T-Box transcriptional activators downstream of these gradients will be tested in T-box mutant backgrounds and by transient over-expression. These findings will be used to test and develop mathematical models of the segmentation clock.

View the original record at the funder ↗

Researchers

Andrew Oates (EPMC Awardee)

Related Research

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Post transcriptional Regulation of Oscillatory clock gene expression during somitogenesis
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Original classification

Senior Research Fellowship Basic

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.