Mechanics and Genetics of Embryonic Development group, Institut Curie, PSL Research University, CNRS, UMR168, Inserm, Marie Curie Univ Paris 06, Institut Curie, 11 rue Pierre et Marie Curie, 75005 Paris, France.
Univ. Grenoble Alpes, Inst NEEL, F-38042 Grenoble, France.
Nat Commun. 2017 Jan 23;8:13883. doi: 10.1038/ncomms13883.
Animal development consists of a cascade of tissue differentiation and shape change. Associated mechanical signals regulate tissue differentiation. Here we demonstrate that endogenous mechanical cues also trigger biochemical pathways, generating the active morphogenetic movements shaping animal development through a mechanotransductive cascade of Myo-II medio-apical stabilization. To mimic physiological tissue deformation with a cell scale resolution, liposomes containing magnetic nanoparticles are injected into embryonic epithelia and submitted to time-variable forces generated by a linear array of micrometric soft magnets. Periodic magnetically induced deformations quantitatively phenocopy the soft mechanical endogenous snail-dependent apex pulsations, rescue the medio-apical accumulation of Rok, Myo-II and subsequent mesoderm invagination lacking in sna mutants, in a Fog-dependent mechanotransductive process. Mesoderm invagination then activates Myo-II apical accumulation, in a similar Fog-dependent mechanotransductive process, which in turn initiates endoderm invagination. This reveals the existence of a highly dynamic self-inductive cascade of mesoderm and endoderm invaginations, regulated by mechano-induced medio-apical stabilization of Myo-II.
动物发育由一系列组织分化和形态变化组成。相关的机械信号调节组织分化。在这里,我们证明内源性机械线索也会触发生化途径,通过 Myo-II 中顶稳定的机械转导级联产生主动形态发生运动,从而塑造动物发育。为了用细胞尺度分辨率模拟生理组织变形,将含有磁性纳米颗粒的脂质体注入胚胎上皮,并通过微尺度软磁铁的线性阵列施加时变力。周期性的磁诱导变形定量模拟了软机械内源性蜗牛依赖性顶端脉冲,挽救了 Rok、Myo-II 的中顶积累,以及 sna 突变体中缺乏的中胚层内陷,这是一个依赖 Fog 的机械转导过程。随后,中胚层内陷激活了 Myo-II 的顶端积累,这是一个类似的依赖 Fog 的机械转导过程,它反过来又引发内胚层内陷。这表明存在一个高度动态的自我诱导中胚层和内胚层内陷级联,由 Myo-II 的机械诱导中顶稳定调节。