Oscillatory contractile forces refine endothelial cell-cell interactions for continuous lumen formation governed by Heg1/Ccm1.

Autor: Yin J; Department of Cell Biology, Biozentrum, University of Basel, Spitalstrasse 41, Basel, 4056, Switzerland. jianmin.yin@unibas.ch., Maggi L; Department of Cell Biology, Biozentrum, University of Basel, Spitalstrasse 41, Basel, 4056, Switzerland., Wiesner C; Department of Cell Biology, Biozentrum, University of Basel, Spitalstrasse 41, Basel, 4056, Switzerland., Affolter M; Department of Cell Biology, Biozentrum, University of Basel, Spitalstrasse 41, Basel, 4056, Switzerland. markus.affolter@unibas.ch., Belting HG; Department of Cell Biology, Biozentrum, University of Basel, Spitalstrasse 41, Basel, 4056, Switzerland. heinz-georg.belting@unibas.ch.
Jazyk: angličtina
Zdroj: Angiogenesis [Angiogenesis] 2024 Nov; Vol. 27 (4), pp. 845-860. Date of Electronic Publication: 2024 Sep 09.
DOI: 10.1007/s10456-024-09945-5
Abstrakt: The formation and organization of complex blood vessel networks rely on various biophysical forces, yet the mechanisms governing endothelial cell-cell interactions under different mechanical inputs are not well understood. Using the dorsal longitudinal anastomotic vessel (DLAV) in zebrafish as a model, we studied the roles of multiple biophysical inputs and cerebral cavernous malformation (CCM)-related genes in angiogenesis. Our research identifies heg1 and krit1 (ccm1) as crucial for the formation of endothelial cell-cell interfaces during anastomosis. In mutants of these genes, cell-cell interfaces are entangled with fragmented apical domains. A Heg1 live reporter demonstrated that Heg1 is dynamically involved in the oscillatory constrictions along cell-cell junctions, whilst a Myosin live reporter indicated that heg1 and krit1 mutants lack actomyosin contractility along these junctions. In wild-type embryos, the oscillatory contractile forces at junctions refine endothelial cell-cell interactions by straightening junctions and eliminating excessive cell-cell interfaces. Conversely, in the absence of junctional contractility, the cell-cell interfaces become entangled and prone to collapse in both mutants, preventing the formation of a continuous luminal space. By restoring junctional contractility via optogenetic activation of RhoA, contorted junctions are straightened and disentangled. Additionally, haemodynamic forces complement actomyosin contractile forces in resolving entangled cell-cell interfaces in both wild-type and mutant embryos. Overall, our study reveals that oscillatory contractile forces governed by Heg1 and Krit1 are essential for maintaining proper endothelial cell-cell interfaces and thus for the formation of a continuous luminal space, which is essential to generate a functional vasculature.
Competing Interests: Declarations Competing interests The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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