Distance between AER and ZPA is defined by feed-forward loop and is stabilized by their feedback loop in vertebrate limb bud

Tsuyoshi Hirashima, Yoh Iwasa, Yoshihiro Morishita

研究成果: Contribution to journalArticle査読

20 被引用数 (Scopus)

抄録

In the development of organs, multiple morphogen sources are often involved, and interact with each other. For example, the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) are major morphogen sources in the limb bud formation of vertebrates. Fgf expression in the AER and Shh expression in the ZPA are maintained by their positive feedback regulation mediated by diffusible molecules, FGF and SHH. A recent experimental observation suggests that the FGF-signal regulates the Shh expression in a feed-forward manner with activation and repression regulatory pathways. We study the coupled dynamics of Shh expression in the ZPA and Fgf expression in the AER, and the relationship of the relative position between AER and ZPA. We first show that with the feed-forward regulation only, the peak of ZPA activity can be formed distant from the AER as observed experimentally. Then, we clarify that the robustness of the ZPA spatial pattern to changes in system parameters is enhanced by adding the feedback regulation between the AER and the ZPA. Furthermore, sensitivity analysis shows that there exists the optimal feedback strength where the robustness is the most improved.

本文言語英語
ページ(範囲)438-459
ページ数22
ジャーナルBulletin of Mathematical Biology
70
2
DOI
出版ステータス出版済み - 2 1 2008

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 免疫学
  • 数学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 薬理学
  • 環境科学(全般)
  • 農業および生物科学(全般)
  • 計算理論と計算数学

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