RESUMEN
Axial development of mammals involves coordinated morphogenetic events, including axial elongation, somitogenesis, and neural tube formation. To gain insight into the signals controlling the dynamics of human axial morphogenesis, we generated axially elongating organoids by inducing anteroposterior symmetry breaking of spatially coupled epithelial cysts derived from human pluripotent stem cells. Each organoid was composed of a neural tube flanked by presomitic mesoderm sequentially segmented into somites. Periodic activation of the somite differentiation gene MESP2 coincided in space and time with anteriorly traveling segmentation clock waves in the presomitic mesoderm of the organoids, recapitulating critical aspects of somitogenesis. Timed perturbations demonstrated that FGF and WNT signaling play distinct roles in axial elongation and somitogenesis, and that FGF signaling gradients drive segmentation clock waves. By generating and perturbing organoids that robustly recapitulate the architecture of multiple axial tissues in human embryos, this work offers a means to dissect mechanisms underlying human embryogenesis.
Asunto(s)
Desarrollo Embrionario , Mesodermo , Somitos , Animales , Humanos , Tipificación del Cuerpo , Regulación del Desarrollo de la Expresión Génica , Mamíferos/genética , Mesodermo/fisiología , Morfogénesis , Vía de Señalización Wnt , Organoides/metabolismoRESUMEN
Growing tissue and bacterial colonies are active matter systems where cell divisions and cellular motion generate active stress. Although they operate in the non-equilibrium regime, these biological systems can form large-scale ordered structures. How mechanical instabilities drive the dynamics of active matter systems and form ordered structures are not well understood. Here, we use chaining Bacillus subtilis, also known as a biofilm, to study the relation between mechanical instabilities and nematic ordering. We find that bacterial biofilms have intrinsic length scales above which a series of mechanical instabilities occur. Localized stress and friction drive buckling and edge instabilities which further create nematically aligned structures and topological defects. We also observe that topological defects control stress distribution and initiate the formation of sporulation sites by creating three-dimensional structures. In this study we propose an alternative active matter platform to study the essential roles of mechanics in growing biological tissue.