PUBLICATION
Periodic inhibition of Erk activity drives sequential somite segmentation
- Authors
- Simsek, M.F., Chandel, A.S., Saparov, D., Zinani, O.Q.H., Clason, N., Özbudak, E.M.
- ID
- ZDB-PUB-221216-20
- Date
- 2022
- Source
- Nature 613(7942): 153-159 (Journal)
- Registered Authors
- Simsek, Muhammed
- Keywords
- none
- MeSH Terms
-
- Animals
- Basic Helix-Loop-Helix Transcription Factors/metabolism
- Biological Clocks
- Body Patterning*
- Extracellular Signal-Regulated MAP Kinases*/antagonists & inhibitors
- Extracellular Signal-Regulated MAP Kinases*/metabolism
- Gene Expression Regulation, Developmental
- Periodicity*
- Somites*/drug effects
- Somites*/embryology
- Somites*/enzymology
- Somites*/metabolism
- Zebrafish*/embryology
- Zebrafish*/metabolism
- Zebrafish Proteins*/antagonists & inhibitors
- Zebrafish Proteins*/metabolism
- PubMed
- 36517597 Full text @ Nature
Citation
Simsek, M.F., Chandel, A.S., Saparov, D., Zinani, O.Q.H., Clason, N., Özbudak, E.M. (2022) Periodic inhibition of Erk activity drives sequential somite segmentation. Nature. 613(7942):153-159.
Abstract
Sequential segmentation creates modular body plans of diverse metazoan embryos1-4. Somitogenesis establishes the segmental pattern of the vertebrate body axis. A molecular segmentation clock in the presomitic mesoderm sets the pace of somite formation4. However, how cells are primed to form a segment boundary at a specific location remains unclear. Here we developed precise reporters for the clock and double-phosphorylated Erk (ppErk) gradient in zebrafish. We show that the Her1-Her7 oscillator drives segmental commitment by periodically lowering ppErk, therefore projecting its oscillation onto the ppErk gradient. Pulsatile inhibition of the ppErk gradient can fully substitute for the role of the clock, and kinematic clock waves are dispensable for sequential segmentation. The clock functions upstream of ppErk, which in turn enables neighbouring cells to discretely establish somite boundaries in zebrafish5. Molecularly divergent clocks and morphogen gradients were identified in sequentially segmenting species3,4,6-8. Our findings imply that versatile clocks may establish sequential segmentation in diverse species provided that they inhibit gradients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping