RNA–Protein Dynamics of the Segmentation Clock and Its Implications in Developmental Disorders
6 affiliations
- 1Department of Neurosurgical Engineering, Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-8575, Japan
- 2Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, IMU University, Kuala Lumpur 57000, Malaysia
- 3Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- 4Department of Medical Science and Innovation, Institute of Medical Research, Tohoku University, Sendai 980-8574, Japan
- 5Department of Translational Neuroscience, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
- 6Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
Abstract
Somitogenesis is orchestrated by the segmentation clock, a highly conserved developmental oscillator that generates periodic gene expression waves to establish precise somite boundaries along the vertebrate body axis. While transcriptional feedback circuits and signaling gradients are recognized as central determinants of clock dynamics, accumulating evidence indicates that RNA-centered regulation provides an important layer of temporal control. We therefore focus primarily on established RNA-regulatory processes, including nascent RNA synthesis, pre-mRNA processing, transcript stability and degradation, and translational control, and examine how these processes interact with protein turnover and intercellular signaling to shape oscillation period, amplitude, and synchronization. Because the molecular implementation of the clock differs among vertebrates, we distinguish species-specific systems throughout: mouse studies primarily define hairy and enhancer of split 1 (Hes) 7/lunatic fringe (Lfng)/Delta-like canonical Notch ligand (Dll) 1 dynamics, zebrafish studies define Hes-related bHLH transcriptional repressor (her) 1/her7/deltaC/deltaD dynamics, chick studies established cyclic c-hairy1/lfng expression, and human HES7/LFNG dynamics are examined mainly in stem-cell-derived presomitic mesoderm (PSM) models. These mechanisms are used to formulate experimentally testable hypotheses about phase-dependent RNA stability, translation, and developmental state transitions. Together, the segmentation clock provides a quantitative framework for distinguishing established RNA–protein mechanisms from emerging RNA-regulatory hypotheses and for understanding how their disruption may contribute to congenital vertebral disorders.
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BibTeX
@article{tan2026rnaprotein,
title = {{RNA–Protein Dynamics of the Segmentation Clock and Its Implications in Developmental Disorders}},
author = {Willem B. Jay Tan and Ami Kobayashi and Kuniyasu Niizuma},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209199},
url = {https://www.mdpi.com/1422-0067/27/20/9199},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - RNA–Protein Dynamics of the Segmentation Clock and Its Implications in Developmental Disorders
AU - Willem B. Jay Tan
AU - Ami Kobayashi
AU - Kuniyasu Niizuma
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209199
UR - https://www.mdpi.com/1422-0067/27/20/9199
AB - Somitogenesis is orchestrated by the segmentation clock, a highly conserved developmental oscillator that generates periodic gene expression waves to establish precise somite boundaries along the vertebrate body axis. While transcriptional feedback circuits and signaling gradients are recognized as central determinants of clock dynamics, accumulating evidence indicates that RNA-centered regulation provides an important layer of temporal control. We therefore focus primarily on established RNA-regulatory processes, including nascent RNA synthesis, pre-mRNA processing, transcript stability and degradation, and translational control, and examine how these processes interact with protein turnover and intercellular signaling to shape oscillation period, amplitude, and synchronization. Because the molecular implementation of the clock differs among vertebrates, we distinguish species-specific systems throughout: mouse studies primarily define hairy and enhancer of split 1 (Hes) 7/lunatic fringe (Lfng)/Delta-like canonical Notch ligand (Dll) 1 dynamics, zebrafish studies define Hes-related bHLH transcriptional repressor (her) 1/her7/deltaC/deltaD dynamics, chick studies established cyclic c-hairy1/lfng expression, and human HES7/LFNG dynamics are examined mainly in stem-cell-derived presomitic mesoderm (PSM) models. These mechanisms are used to formulate experimentally testable hypotheses about phase-dependent RNA stability, translation, and developmental state transitions. Together, the segmentation clock provides a quantitative framework for distinguishing established RNA–protein mechanisms from emerging RNA-regulatory hypotheses and for understanding how their disruption may contribute to congenital vertebral disorders.
SN - 1422-0067
ER -