Retrograde ERK activation waves drive base-to-apex multicellular flow in murine cochlear duct morphogenesis

抄録

A notable example of spiral architecture in organs is the mammalian cochlear duct, where the morphology is critical for hearing function. Genetic studies have revealed necessary signaling molecules, but it remains unclear how cellular dynamics generate elongating, bending, and coiling of the cochlear duct. Here, we show that extracellular signal-regulated kinase (ERK) activation waves control collective cell migration during the murine cochlear duct development using deep tissue live-cell imaging, Förster resonance energy transfer (FRET)-based quantitation, and mathematical modeling. Long-term FRET imaging reveals that helical ERK activation propagates from the apex duct tip concomitant with the reverse multicellular flow on the lateral side of the developing cochlear duct, resulting in advection-based duct elongation. Moreover, model simulations, together with experiments, explain that the oscillatory wave trains of ERK activity and the cell flow are generated by mechanochemical feedback. Our findings propose a regulatory mechanism to coordinate the multicellular behaviors underlying the duct elongation during development.

うずまき管の伸⻑を司る分子活性と細胞群の波を発見 --綱引きによる細胞群の流れと臓器の成長--. 京都大学プレスリリース. 2021-03-09.

収録刊行物

  • eLife

    eLife 10 e61092-, 2021

    eLife Sciences Publications, Ltd

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