Iterative joints are a hallmark of the tetrapod limb, and their positioning is a key step during limb development. Whilst the molecular regulation of joint formation is well-studied, it remains ...unclear what controls the location, number and orientation (i.e. the pattern) of joints within each digit. Here we propose the dot-stripe mechanism for joint patterning, comprising two coupled Turing systems inspired by published gene expression patterns. Our model can explain normal joint morphology in wildtype limbs, hyperphalangy in cetacean flippers, mutant phenotypes with misoriented joints and suggests a reinterpretation of the polydactylous Ichthyosaur fins as a polygonal joint lattice. By formulating a generic dot-stripe model, describing joint patterns rather than molecular joint markers, we demonstrate that the insights from the model should apply regardless of the biological specifics of the underlying mechanism, thus providing a unifying framework to interrogate joint patterning in the tetrapod limb.
Tissue folds are structural motifs critical to organ function. In the intestine, bending of a flat epithelium into a periodic pattern of folds gives rise to villi, finger-like protrusions that enable ...nutrient absorption. However, the molecular and mechanical processes driving villus morphogenesis remain unclear. Here, we identify an active mechanical mechanism that simultaneously patterns and folds the intestinal epithelium to initiate villus formation. At the cellular level, we find that PDGFRA+ subepithelial mesenchymal cells generate myosin II-dependent forces sufficient to produce patterned curvature in neighboring tissue interfaces. This symmetry-breaking process requires altered cell and extracellular matrix interactions that are enabled by matrix metalloproteinase-mediated tissue fluidization. Computational models, together with in vitro and in vivo experiments, revealed that these cellular features manifest at the tissue level as differences in interfacial tensions that promote mesenchymal aggregation and interface bending through a process analogous to the active dewetting of a thin liquid film.
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•Mesenchymal aggregates generate forces that fold the mammalian intestinal epithelium•Active and fluid-like properties of aggregates program tissue geometry and pattern•Matrix metalloproteinases fluidize the subepithelial mesenchyme to initiate aggregation•Mesenchymal patterning conceptually resembles water dewetting from a hydrophobic surface
Subepithelial mesenchyme behaves like a dewetting fluid to pattern and fold the intestinal epithelium, initiating the formation of villi.
Zoonotic diseases will maintain a high level of public policy attention in the coming decades. From the spectre of a global pandemic to anxieties over agricultural change, urbanization, social ...inequality and threats to natural ecosystems, effectively preparing and responding to endemic and emerging diseases will require technological, institutional and social innovation. Much current discussion emphasizes the need for a 'One Health' approach: bridging disciplines and sectors to tackle these complex dynamics. However, as attention has increased, so too has an appreciation of the practical challenges in linking multi-disciplinary, multi-sectoral research with policy, action and impact. In this commentary paper, we reflect on these issues with particular reference to the African sub-continent. We structure the themes of our analysis on the existing literature, expert opinion and 11 interviews with leading One Health scholars and practitioners, conducted at an international symposium in 2016. We highlight a variety of challenges in research and knowledge production, in the difficult terrain of implementation and outreach, and in the politicized nature of decision-making and priority setting. We then turn our attention to a number of strategies that might help reconfigure current pathways and accepted norms of practice. These include: (i) challenging scientific expertise; (ii) strengthening national multi-sectoral coordination; (iii) building on what works; and (iv) re-framing policy narratives. We argue that bridging the research-policy-action interface in Africa, and better connecting zoonoses, ecosystems and well-being in the twenty-first century, will ultimately require greater attention to the democratization of science and public policy. This article is part of the themed issue 'One Health for a changing world: zoonoses, ecosystems and human well-being'.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The development of multicellular organisms proceeds through a series of morphogenetic and cell-state transitions, transforming homogeneous zygotes into complex adults by a process of ...self-organization. Many of these transitions are achieved by spontaneous symmetry breaking mechanisms, allowing cells and tissues to acquire pattern and polarity by virtue of local interactions without an upstream supply of information. The combined work of theory and experiment has elucidated how these systems break symmetry during developmental transitions. Given such transitions are multiple and their temporal ordering is crucial, an equally important question is how these developmental transitions are coordinated in time. Using a minimal mass-conserved substrate-depletion model for symmetry breaking as our case study, we elucidate mechanisms by which cells and tissues can couple reaction-diffusion driven symmetry breaking to the timing of developmental transitions, arguing that the dependence of patterning mode on system size may be a generic principle by which developing organisms measure time. By analyzing different regimes of our model, simulated on growing domains, we elaborate three distinct behaviours, allowing for clock-, timer-, or switch-like dynamics. By relating these behaviours to experimentally documented case studies of developmental timing, we provide a minimal conceptual framework to interrogate how developing organisms coordinate developmental transitions.
