Mechanical force-driven cell competition ensures robust morphogen gradient formation

Aoki, Kana; Ishitani, Tohru

doi:https://doi.org/10.1016/j.semcdb.2025.103607

Mechanical force-driven cell competition ensures robust morphogen gradient formation

Aoki, Kana; Ishitani, Tohru

Seminars in Cell and Developmental Biology, 2025, 170, 103607

アクセス数:135件（2025-07-22 21:05 集計）

固定URL: https://hdl.handle.net/11094/101393

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タイトル	Mechanical force-driven cell competition ensures robust morphogen gradient formation
著者	NRID 1000070904738 1000070904738 researchmap permalink kanaaoki kanaaoki Scopus Author ID 57188650523 57188650523 著者名 Aoki, Kana
著者	NRID 1000040448428 1000040448428 ORCID 0000-0002-6200-7043 0000-0002-6200-7043 researchmap permalink read0148831 read0148831 Scopus Author ID 8079317200 8079317200 著者名 Ishitani, Tohru
キーワード等	Morphogen
	Cell competition
	Mechanical force
	Cadherin
	Wnt
	Shh
	Piezo
内容	Aoki K., Ishitani T.. Mechanical force-driven cell competition ensures robust morphogen gradient formation. Seminars in Cell and Developmental Biology 170, 103607 (2025); https://doi.org/10.1016/j.semcdb.2025.103607.
抄録	Morphogen gradients provide positional data and maintain tissue patterns by instructing cells to adopt distinct fates. In contrast, morphogen gradient-forming tissues undergo dynamic morphogenetic movements that generate mechanical forces and can disturb morphogen signal transduction. However, the interactions between morphogen gradients and these forces remain largely unknown. In this study, we described how mechanical force-mediated cell competition corrects noisy morphogen gradients to ensure robust tissue patterns. The Wnt/β-catenin morphogen gradient—that patterns the embryonic anterior-posterior axis—generates cadherin-actomyosin interaction-mediated intercellular tension gradients—termed mechano-gradients. Naturally generated unfit cells that produce noisy Wnt/β-catenin gradients induce local deformation of the mechano-gradients. Neighboring fit cells sense this deformation, resulting in the activation of Piezo family mechanosensitive calcium channels and secretion of annexinA1, which specifically kills unfit cells to recover morphogen gradients. Therefore, mechanical force-mediated cell competition between the morphogen-receiver cells supports robust gradient formation. Additionally, we discuss the potential roles of mechanical force-driven cell competition in other contexts, including organogenesis and cancer.
出版者	Elsevier Ltd
収録物名	Seminars in Cell and Developmental Biology
巻(号)	170
ページ	103607
刊行年月	2025-04-13
言語	英語
ハンドルURL	https://hdl.handle.net/11094/101393
PISSN	10849521
eISSN	10963634
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1016/j.semcdb.2025.103607
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Seminars in Cell and Developmental Biology. 2025, 170, p. 103607
DC.title	Mechanical force-driven cell competition ensures robust morphogen gradient formation
DC.creator	Aoki, Kana
DC.creator	Ishitani, Tohru
DC.publisher	Elsevier Ltd
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-04-13
DC.identifier	https://doi.org/10.1016/j.semcdb.2025.103607
DC.subject	Morphogen
	Cell competition
	Mechanical force
	Cadherin
	Wnt
	Shh
	Piezo
DC.description	Aoki K., Ishitani T.. Mechanical force-driven cell competition ensures robust morphogen gradient formation. Seminars in Cell and Developmental Biology 170, 103607 (2025); https://doi.org/10.1016/j.semcdb.2025.103607.
DCTERMS.abstract	Morphogen gradients provide positional data and maintain tissue patterns by instructing cells to adopt distinct fates. In contrast, morphogen gradient-forming tissues undergo dynamic morphogenetic movements that generate mechanical forces and can disturb morphogen signal transduction. However, the interactions between morphogen gradients and these forces remain largely unknown. In this study, we described how mechanical force-mediated cell competition corrects noisy morphogen gradients to ensure robust tissue patterns. The Wnt/β-catenin morphogen gradient—that patterns the embryonic anterior-posterior axis—generates cadherin-actomyosin interaction-mediated intercellular tension gradients—termed mechano-gradients. Naturally generated unfit cells that produce noisy Wnt/β-catenin gradients induce local deformation of the mechano-gradients. Neighboring fit cells sense this deformation, resulting in the activation of Piezo family mechanosensitive calcium channels and secretion of annexinA1, which specifically kills unfit cells to recover morphogen gradients. Therefore, mechanical force-mediated cell competition between the morphogen-receiver cells supports robust gradient formation. Additionally, we discuss the potential roles of mechanical force-driven cell competition in other contexts, including organogenesis and cancer.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	101393
citation_title	Mechanical force-driven cell competition ensures robust morphogen gradient formation
citation_author	Aoki, Kana
citation_author	Ishitani, Tohru
citation_publisher	Elsevier Ltd
citation_language	英語
citation_date	2025-04-13
citation_journal_title	Seminars in Cell and Developmental Biology
citation_volume	170
citation_firstpage	103607
citation_doi	https://doi.org/10.1016/j.semcdb.2025.103607
citation_public_url	https://hdl.handle.net/11094/101393

Mechanical force-driven cell competition ensures robust morphogen gradient formation

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