Force-dependent stabilization of apical actomyosin by Lmo7 during vertebrate neurulation

脊椎动物神经管形成过程中,Lmo7 对顶端肌动蛋白的力依赖性稳定作用

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Abstract

Coordinated control of actomyosin contractility is essential for epithelial morphogenesis, including vertebrate neural tube closure. Lim domain only 7 (Lmo7) is a force-sensitive regulator of contractility that binds non-muscle myosin II (NMII) heavy chain to initiate apical constriction (AC) during Xenopus neural tube closure. Lmo7 is not required for actomyosin pulsatile activity or changes in the junction length in the intercalating cells during anteroposterior axis elongation. However, Lmo7 knockdown fails to stabilize actomyosin at the apical cortex at the onset of neural tube folding. Gain-of-function approach in gastrula ectoderm confirms a role for Lmo7 in actomyosin stabilization. Mechanistically, force-dependent dephosphorylation of Ser355 in the Lmo7 myosin binding domain enhances Lmo7 binding to NMII and increases NMII abundance at the apical cortex. Notably, initially homogeneous expression of Lmo7 in ectoderm cells progressively leads to apical domain heterogeneity that tightly correlates with Lmo7 levels, arguing for a positive feedback regulation between mechanical forces and Lmo7 activity. We propose that the force-dependent binding of Lmo7 to NMII stabilizes both proteins at the apical cortex, triggering enhanced apical constriction.

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