論文

査読有り 国際誌
2019年2月4日

Noise-resistant developmental reproducibility in vertebrate somite formation.

PLoS computational biology
  • Honda Naoki
  • ,
  • Ryutaro Akiyama
  • ,
  • Dini Wahyu Kartika Sari
  • ,
  • Shin Ishii
  • ,
  • Yasumasa Bessho
  • ,
  • Takaaki Matsui

15
2
開始ページ
e1006579
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pcbi.1006579

The reproducibility of embryonic development is remarkable, although molecular processes are intrinsically stochastic at the single-cell level. How the multicellular system resists the inevitable noise to acquire developmental reproducibility constitutes a fundamental question in developmental biology. Toward this end, we focused on vertebrate somitogenesis as a representative system, because somites are repeatedly reproduced within a single embryo whereas such reproducibility is lost in segmentation clock gene-deficient embryos. However, the effect of noise on developmental reproducibility has not been fully investigated, because of the technical difficulty in manipulating the noise intensity in experiments. In this study, we developed a computational model of ERK-mediated somitogenesis, in which bistable ERK activity is regulated by an FGF gradient, cell-cell communication, and the segmentation clock, subject to the intrinsic noise. The model simulation generated our previous in vivo observation that the ERK activity was distributed in a step-like gradient in the presomitic mesoderm, and its boundary was posteriorly shifted by the clock in a stepwise manner, leading to regular somite formation. Here, we showed that this somite regularity was robustly maintained against the noise. Removing the clock from the model predicted that the stepwise shift of the ERK activity occurs at irregular timing with irregular distance owing to the noise, resulting in somite size variation. This model prediction was recently confirmed by live imaging of ERK activity in zebrafish embryos. Through theoretical analysis, we presented a mechanism by which the clock reduces the inherent somite irregularity observed in clock-deficient embryos. Therefore, this study indicates a novel role of the segmentation clock in noise-resistant developmental reproducibility.

リンク情報
DOI
https://doi.org/10.1371/journal.pcbi.1006579
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30716091
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361423
URL
https://www.biorxiv.org/content/early/2018/01/15/247783
ID情報
  • DOI : 10.1371/journal.pcbi.1006579
  • PubMed ID : 30716091
  • PubMed Central 記事ID : PMC6361423

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