2024-04-03 カリフォルニア大学サンタバーバラ校(UCSB)
◆これまで、これらのシグナリングセンターは科学に知られていましたが、個々の細胞がどのようにしてオーガナイザーに変化するかは謎でした。
◆研究では、細胞が組織化される際に、文字通りオーガナイザーになるように機械的圧迫を受けていることが発見されました。このメカニズムを理解することで、先天性奇形を持つ子供たちの問題についての理解が深まる可能性があります。
<関連情報>
- https://news.ucsb.edu/2024/021397/pressure-determines-which-embryonic-cells-become-organizers
- https://www.nature.com/articles/s41556-024-01380-4
哺乳類の臓器発生において、増殖主導型の機械的圧迫がシグナル伝達中心の形成を誘導する Proliferation-driven mechanical compression induces signalling centre formation during mammalian organ development
Neha Pincha Shroff,Pengfei Xu,Sangwoo Kim,Elijah R. Shelton,Ben J. Gross,Yucen Liu,Carlos O. Gomez,Qianlin Ye,Tingsheng Yu Drennon,Jimmy K. Hu,Jeremy B. A. Green,Otger Campàs & Ophir D. Klein
Nature Cell Biology Published:03 April 2024
DOI:https://doi.org/10.1038/s41556-024-01380-4
Abstract
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.
