Noise in the Vertebrate Segmentation Clock Is Boosted by Time Delays but Tamed by Notch Signaling

Cell Reports
Sevdenur KeskinErtuğrul M Özbudak

Abstract

Taming cell-to-cell variability in gene expression is critical for precise pattern formation during embryonic development. To investigate the source and buffering mechanism of expression variability, we studied a biological clock, the vertebrate segmentation clock, controlling the precise spatiotemporal patterning of the vertebral column. By counting single transcripts of segmentation clock genes in zebrafish, we show that clock genes have low RNA amplitudes and expression variability is primarily driven by gene extrinsic sources, which is suppressed by Notch signaling. We further show that expression noise surprisingly increases from the posterior progenitor zone to the anterior segmentation and differentiation zone. Our computational model reproduces the spatial noise profile by incorporating spatially increasing time delays in gene expression. Our results, suggesting that expression variability is controlled by the balance of time delays and cell signaling in a vertebrate tissue, will shed light on the accuracy of natural clocks in multi-cellular systems and inspire engineering of robust synthetic oscillators.

Citations

Sep 19, 2019·Journal of the Royal Society, Interface·Jonas S JuulSandeep Krishna
Jul 17, 2020·Development·Christoph ZechnerCaren Norden
Jan 10, 2021·Journal of Fungi·François DanionJean-Paul Latgé
Dec 29, 2020·Nature·Oriana Q H ZinaniErtuğrul M Özbudak
Mar 31, 2019·Developmental Biology·Rajasekaran Bhavna
Jul 16, 2019·Developmental Biology·Olivier F Venzin, Andrew C Oates
Jun 1, 2021·Interface Focus·Erik Clark
Aug 12, 2021·Trends in Genetics : TIG·Oriana Q H ZinaniErtuğrul M Özbudak
Nov 15, 2021·Biophysical Journal·Supravat Dey, Abhyudai Singh

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Methods Mentioned

BETA
smFISH
transgenic
in vitro transcription

Key Resources (RRID) Mentioned

AB_221570
AB_2576217
SCR_007370
SCR_008394
SCR_001622
SCR_003070
SCR_002798

Software Mentioned

StepOne
Imaris
smFISH
ImageJ
Axiovision

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