2025年新着論文 53　生体力学シグナル分野から論文が発表されました

Endothelial-zippering proceeds by sensing heartbeat-driven force through cadherin-6 during heart-vessel connection in zebrafish

Dev Cell. 2025 Nov 11:S1534-5807(25)00662-8. doi: 10.1016/j.devcel.2025.10.011. Online ahead of print.

Authors

Moe Fukumoto¹, Haruko Watanabe-Takano², Hajime Fukui³, Ayano Chiba⁴, Keisuke Sako⁵, Hiroyuki Nakajima¹, Naoki Mochizuki⁶

Affiliations

¹ Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shimmachi, Suita 564-8565, Osaka, Japan.
² Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shimmachi, Suita 564-8565, Osaka, Japan; Department of Molecular Pathophysiology, Institute of Advanced Medical Sciences, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
³ Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shimmachi, Suita 564-8565, Osaka, Japan; Division of Biomechanics and Signaling, Institute of Advanced Medical Sciences Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
⁴ Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shimmachi, Suita 564-8565, Osaka, Japan; Department of Pharmacology, Yamagata University School of Medicine, 2-2-2 Idanishi, Yamagata 990-9585, Japan.
⁵ Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shimmachi, Suita 564-8565, Osaka, Japan; Department of Anatomy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
⁶ Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-shimmachi, Suita 564-8565, Osaka, Japan. Electronic address: mochizuki@ncvc.go.jp.

PMID: 41223859
DOI: 10.1016/j.devcel.2025.10.011

Abstract

The connection between the heart and great vessels established during embryogenesis is essential for circulation. However, how great veins adhere to the endocardium lining the inside lumen of the beating heart remains unknown. Here, using zebrafish, we demonstrate that the endocardium and great veins are sealed in a zipper-closing manner outside the beating heart. The gradual elongation of the endocardium, driven by convergent extension, organized this adhesion by pulling venous endothelial cells (ECs) along the anterior-posterior axis. Time-specific manipulation of the heart rate revealed that this endocardial elongation proceeds against heartbeat-driven force. From time-lapse imaging of adherens junctions, which would counterbalance mechanical forces, we found a specific contribution of cadherin-6 instead of cadherin-5 in sensing endocardium-specific mechanical force. This specificity was confirmed by the depletion of cadherin-6 that caused endocardium deformation. Altogether, we propose that cadherin-6-mediated EC-zippering updates the understanding of cadherin usage in dynamic morphogenesis.

Keywords: cadherin; common cardinal vein; convergent extension; endocardium; heartbeat; intercellular adhesion; zippering.

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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