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

journal contribution
posted on 2023-05-23, 02:42 authored by Sevdenur Keskin, Gnanapackiam S Devakanmalai, Soo Bin Kwon, Ha VuHa Vu, Qiyuan Hong, Yin Yeng Lee, Mohammad Soltani, Abhyudai Singh, Ahmet Ay, Ertugrul M Ozbudak
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.

History

Journal

CELL REPORTS

Volume

23

Pagination

2175-+

Location

United States

ISSN

2211-1247

eISSN

2211-1247

Language

English

Publication classification

C1.1 Refereed article in a scholarly journal

Issue

7

Publisher

CELL PRESS