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Self-organization guides robust, spatiotemporally ordered formation of complex tissues and ultimately whole organisms. While products of gene expression serve as building blocks of living matter, how these interact to give rise to tissues of distinct patterns and function remains a central question in biology. Tissue self-organization relies on dynamic interactions between constituents spanning a range of spatiotemporal scales with tuneable chemical and mechanical parameters. This review highlights recent studies dissecting mechanisms of these interactions. We propose that feedback interactions between cell polarity, mechanics, and fate are a key principle underlying tissue self-organization. We also provide a glimpse into how such processes can be studied in future endeavors.
Figure 1. Feedback Interactions between Polarity, Mechanics and Fate as a Principle Underlying Tissue Self-organization. These three parameters operate over a broad spatiotemporal spectrum, driving the emergence of increasing biological complexity through self-organizing interactions. We propose that the tripartite relationship between cell polarity, mechanics, and fate comprise the core foundation of multicellular self-organization.
Figure 2. Self-organization Spans Multiple Scales. Tissue self-organization relies on interactions between lower level components that range from molecules to cells. (A,B) For example, the inherent structural asymmetry of G-actin molecules (with ‘barbed’ and ‘pointed’ ends) underlies biased regulation of the rate and direction of filament polymerization. (B) Interactions between multiple actin filaments and their geometric arrangement are subject to modulation by regulatory proteins, such as formins and Arp2/3. (C) The specific regulatory proteins involved, geometry, and stability of an intracellular actin network vary according to the functional requirements of the cell. Similar principles apply to microtubule (MT) tracks, another major cytoskeletal component. These are collectively regulated by various polarity components and intracellular signaling pathways to perform a variety of cellular functions, such as directed migration, secretion, absorption and cell shape changes. In particular, asymmetric cytoskeletal arrangements critically underlie apico-basal polarity of epithelial cells. (D) In epithelial tissues, actin networks are coordinated across cells through adherens junctions. This allows mechanical coupling across a sheet of cells, such that shape changes in relatively few cells can be rapidly transmitted across their neighbors to achieve tissue folding. (E) Such cooperative interactions between polarity signals and mechanical forces, mediated by the actin network, underlie morphogenesis of various epithelial structures, such as the neural tube, during development.
Figure 3. Cooperation between Polarity and Mechanics in Development. (A) Establishment of the anterior–posterior (A–P) axis in the Caenorhabditis elegans zygote relies on biochemical interactions between different PAR proteins, as well as advective transport of anterior components through actomyosin-driven cortical flow. Anterior components are initially distributed throughout the cortex, until localized inhibition of contractile actomyosin by the MTOC at the site of sperm entry drives anteriorly directed cortical flow. Anterior polarity components are not passive during transport, but reinforce flow by positive regulation of actomyosin contractility. Polarity-dependent asymmetric division of the zygote segregates the future somatic and germline lineages through selective enrichment of P-granules to the posterior end of the embryo. The anterior daughter cell ‘AB’ is a founder blastomere that will give rise to differentiated progeny, while the posterior ‘P1’ is a germline blastomere. (B) The A–P axis of Drosophila is established as a result of dramatic elongation of the egg within the ovariole. This elongation is dependent on a planar polarized basal actin network and a graded secretion of basement membrane components across the follicle cell epithelium, which underlies egg chamber rotation and anisotropic resistance to growth. Loss of planar cell polarity or connections to the basement membrane lead to ‘round egg’ phenotypes. Maternal effect gene products, such as bicoid and oskar mRNAs, are subsequently localized to the anterior and posterior ends of the egg, respectively. (C) Polarization takes place de novo during the 8-cell stage of mouse embryonic development. Mechanical contact directs the site of apical domain (red) emergence, which in turn modulates spindle pole recruitment and locally reduces cortical contractility. Upon division, differences in polarity and cortical tension bias spatial sorting among cells of the 16-cell stage embryo and subsequently lead to divergence of the extraembryonic [trophectoderm (TE)] and embryonic [inner cell mass (ICM)] lineages, as marked by differential localization of YAP. YAP is nuclear localized in outer cells, while cytoplasmic in inner cells. Cells that are completely internalized at the 16-cell stage are marked by yellow. By the blastocyst stage, the polarized TE (green) surrounds the inner ICM (yellow), demonstrating robust spatial segregation between the two lineages. Such spatial and fate segregation between TE and ICM can be recapitulated in a reduced system from a single blastomere isolated from the 8-cell stage embryo.
