Proliferation-driven mechanical compression induces signalling centre formation during mammalian organ development.

Autor: Shroff NP; Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, CA, USA., Xu P; Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, CA, USA., Kim S; Department of Mechanical Engineering, University of California, Santa Barbara, CA, USA.; Institute of Mechanical Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Shelton ER; Department of Mechanical Engineering, University of California, Santa Barbara, CA, USA., Gross BJ; Department of Mechanical Engineering, University of California, Santa Barbara, CA, USA., Liu Y; Department of Mechanical Engineering, University of California, Santa Barbara, CA, USA., Gomez CO; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA., Ye Q; School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA.; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, USA., Drennon TY; Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, CA, USA., Hu JK; School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA.; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, USA., Green JBA; Centre for Craniofacial Regeneration and Biology, King's College London, London, UK., Campàs O; Department of Mechanical Engineering, University of California, Santa Barbara, CA, USA. otger.campas@tu-dresden.de.; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA. otger.campas@tu-dresden.de.; Cluster of Excellence Physics of Life, TU Dresden, Dresden, Germany. otger.campas@tu-dresden.de.; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany. otger.campas@tu-dresden.de.; Center for Systems Biology Dresden, Dresden, Germany. otger.campas@tu-dresden.de., Klein OD; Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, CA, USA. Ophir.Klein@cshs.org.; Department of Pediatrics, Cedars-Sinai Guerin Children's, Los Angeles, CA, USA. Ophir.Klein@cshs.org.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2024 Apr; Vol. 26 (4), pp. 519-529. Date of Electronic Publication: 2024 Apr 03.
DOI: 10.1038/s41556-024-01380-4
Abstrakt: Localized sources of morphogens, called signalling centres, play a fundamental role in coordinating tissue growth and cell fate specification during organogenesis. However, how these signalling centres are established in tissues during embryonic development is still unclear. Here we show that the main signalling centre orchestrating development of rodent incisors, the enamel knot (EK), is specified by a cell proliferation-driven buildup in compressive stresses (mechanical pressure) in the tissue. Direct mechanical measurements indicate that the stresses generated by cell proliferation are resisted by the surrounding tissue, creating a circular pattern of mechanical anisotropy with a region of high compressive stress at its centre that becomes the EK. Pharmacological inhibition of proliferation reduces stresses and suppresses EK formation, and application of external pressure in proliferation-inhibited conditions rescues the formation of the EK. Mechanical information is relayed intracellularly through YAP protein localization, which is cytoplasmic in the region of compressive stress that establishes the EK and nuclear in the stretched anisotropic cells that resist the pressure buildup around the EK. Together, our data identify a new role for proliferation-driven mechanical compression in the specification of a model signalling centre during mammalian organ development.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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