Control of Modular Tissue Flows Shaping the Embryo in Avian Gastrulation.

Avian gastrulation requires coordinated flows of thousands of cells to form the body plan. We quantified these flows using their fundamental kinematic units: one attractor and two repellers constituting its Dynamic Morphoskeleton (DM). We have also elucidated the mechanistic origin of the attractor, marking the primitive streak (PS), and controlled its shape, inducing gastrulation flows in the chick embryo that are typical of other vertebrates.

A mechanochemical model recapitulates distinct vertebrate gastrulation modes.

During vertebrate gastrulation, an embryo transforms from a layer of epithelial cells into a multilayered gastrula. This process requires the coordinated movements of hundreds to tens of thousands of cells, depending on the organism. In the chick embryo, patterns of actomyosin cables spanning several cells drive coordinated tissue flows.

The evolution of gastrulation morphologies.

During gastrulation, early embryos specify and reorganise the topology of their germ layers. Surprisingly, this fundamental and early process does not appear to be rigidly constrained by evolutionary pressures; instead, the morphology of gastrulation is highly variable throughout the animal kingdom. Recent experimental results demonstrate that it is possible to generate different alternative gastrulation modes in single organisms, such as in early cnidarian, arthropod and vertebrate embryos.

Generating active T1 transitions through mechanochemical feedback.

Convergence-extension in embryos is controlled by chemical and mechanical signalling. A key cellular process is the exchange of neighbours via T1 transitions. We propose and analyse a model with positive feedback between recruitment of myosin motors and mechanical tension in cell junctions.

Reconstruction of distinct vertebrate gastrulation modes via modulation of key cell behaviors in the chick embryo.

The morphology of gastrulation driving the internalization of the mesoderm and endoderm differs markedly among vertebrate species. It ranges from involution of epithelial sheets of cells through a circular blastopore in amphibians to ingression of mesenchymal cells through a primitive streak in amniotes. By targeting signaling pathways controlling critical cell behaviors in the chick embryo, we generated crescent- and ring-shaped mesendoderm territories in which cells can or cannot ingress.

Moving the Research Forward: The Best of British Biology Using the Tractable Model System .

The social amoeba provides an excellent model for research across a broad range of disciplines within biology. The organism diverged from the plant, yeast, fungi and animal kingdoms around 1 billion years ago but retains common aspects found in these kingdoms. has a low level of genetic complexity and provides a range of molecular, cellular, biochemical and developmental biology experimental techniques, enabling multidisciplinary studies to be carried out in a wide range of areas, leading to research breakthroughs.

Effects of spatial confinement on migratory properties of Dictyostelium discoideum cells.

Migratory environments of various eukaryotic cells, such as amoeba, leukocytes and cancer cells, typically involve spatial confinement. Numerous studies have recently emerged, aimed to develop experimental platforms that better recapitulate the characteristics of the cellular microenvironment. Using microfluidic technologies, we show that increasing confinement of Dictyostelium discoideum cells into narrower micro-channels resulted in a significant change in the mode of migration and associated arrangement of the actomyosin cytoskeleton.

Chemotaxis: Active Degradation of Attractant Enables Optimal Maze Navigation.

How signals coordinate and direct chemotaxis is an issue that is actively investigated. A new study shows how the dynamic alteration of chemoattractant flux by chemotaxing cells provides an efficient way to solve complex navigational tasks, including finding the optimal path through a complex maze.

Analysis of barotactic and chemotactic guidance cues on directional decision-making of cells in confined environments.

Neutrophils and dendritic cells when migrating in confined environments have been shown to actuate a directional choice toward paths of least hydraulic resistance (barotaxis), in some cases overriding chemotactic responses. Here, we investigate whether this barotactic response is conserved in the more primitive model organism using a microfluidic chip design. This design allowed us to monitor the behavior of single cells via live imaging when confronted with bifurcating microchannels, presenting different combinations of hydraulic and chemical stimuli.

Cellular processes driving gastrulation in the avian embryo.

Gastrulation consists in the dramatic reorganisation of the epiblast, a one-cell thick epithelial sheet, into a multilayered embryo. In chick, the formation of the internal layers requires the generation of a macroscopic convection-like flow, which involves up to 50,000 epithelial cells in the epiblast. These cell movements locate the mesendoderm precursors into the midline of the epiblast to form the primitive streak.

Dynamic morphoskeletons in development.

Morphogenetic flows in developmental biology are characterized by the coordinated motion of thousands of cells that organize into tissues, naturally raising the question of how this collective organization arises. Using only the kinematics of tissue deformation, which naturally integrates local and global mechanisms along cell paths, we identify the dynamic morphoskeletons behind morphogenesis, i.e.

Measurement of junctional tension in epithelial cells at the onset of primitive streak formation in the chick embryo via non-destructive optical manipulation.

Directional cell intercalations of epithelial cells during gastrulation has, in several organisms, been shown to be associated with a planar cell polarity in the organisation of the actin-myosin cytoskeleton and is postulated to reflect directional tension that drives oriented cell intercalations. We have characterised and applied a recently introduced non-destructive optical manipulation technique to measure the tension in individual epithelial cell junctions of cells in various locations and orientations in the epiblast of chick embryos in the early stages of primitive streak formation. Junctional tension of mesendoderm precursors in the epiblast is higher in junctions oriented in the direction of intercalation than in junctions oriented perpendicular to the direction of intercalation and higher than in junctions of other cells in the epiblast.

Oscillatory cAMP cell-cell signalling persists during multicellular development.

Propagating waves of cAMP, periodically initiated in the aggregation centre, are known to guide the chemotactic aggregation of hundreds of thousands of starving individual cells into multicellular aggregates. Propagating optical density waves, reflecting cell periodic movement, have previously been shown to exist in streaming aggregates, mounds and migrating slugs. Using a highly sensitive cAMP-FRET reporter, we have now been able to measure periodically propagating cAMP waves directly in these multicellular structures.

Active Vertex Model for cell-resolution description of epithelial tissue mechanics.

We introduce an Active Vertex Model (AVM) for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales.

Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons from .

Movement of cells and tissues is a basic biological process that is used in development, wound repair, the immune response to bacterial invasion, tumour formation and metastasis, and the search for food and mates. While some cell movement is random, directed movement stimulated by extracellular signals is our focus here. This involves a sequence of steps in which cells first detect extracellular chemical and/or mechanical signals via membrane receptors that activate signal transduction cascades and produce intracellular signals.

The multicellularity genes of dictyostelid social amoebas.

The evolution of multicellularity enabled specialization of cells, but required novel signalling mechanisms for regulating cell differentiation. Early multicellular organisms are mostly extinct and the origins of these mechanisms are unknown. Here using comparative genome and transcriptome analysis across eight uni- and multicellular amoebozoan genomes, we find that 80% of proteins essential for the development of multicellular Dictyostelia are already present in their unicellular relatives.

Myosin-II-mediated cell shape changes and cell intercalation contribute to primitive streak formation.

Primitive streak formation in the chick embryo involves large-scale highly coordinated flows of more than 100,000 cells in the epiblast. These large-scale tissue flows and deformations can be correlated with specific anisotropic cell behaviours in the forming mesendoderm through a combination of light-sheet microscopy and computational analysis. Relevant behaviours include apical contraction, elongation along the apical-basal axis followed by ingression, and asynchronous directional cell intercalation of small groups of mesendoderm cells.

SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale.

Cytoskeletal dynamics during cell behaviours ranging from endocytosis and exocytosis to cell division and movement is controlled by a complex network of signalling pathways, the full details of which are as yet unresolved. Here we show that SILAC-based proteomic methods can be used to characterize the rapid chemoattractant-induced dynamic changes in the actin-myosin cytoskeleton and regulatory elements on a proteome-wide scale with a second to minute timescale resolution. This approach provides novel insights in the ensemble kinetics of key cytoskeletal constituents and association of known and novel identified binding proteins.

Collective epithelial and mesenchymal cell migration during gastrulation.

Gastrulation, the process that puts the three major germlayers, the ectoderm, mesoderm and endoderm in their correct topological position in the developing embryo, is characterised by extensive highly organised collective cell migration of epithelial and mesenchymal cells. We discuss current knowledge and insights in the mechanisms controlling these cell behaviours during gastrulation in the chick embryo. We discuss several ideas that have been proposed to explain the observed large scale vortex movements of epithelial cells in the epiblast during formation of the primitive streak.

Tumorigenic fragments of APC cause dominant defects in directional cell migration in multiple model systems.

Nonsense mutations that result in the expression of truncated, N-terminal, fragments of the adenomatous polyposis coli (APC) tumour suppressor protein are found in most sporadic and some hereditary colorectal cancers. These mutations can cause tumorigenesis by eliminating β-catenin-binding sites from APC, which leads to upregulation of β-catenin and thereby results in the induction of oncogenes such as MYC. Here we show that, in three distinct experimental model systems, expression of an N-terminal fragment of APC (N-APC) results in loss of directionality, but not speed, of cell motility independently of changes in β-catenin regulation.

Correlating cell behavior with tissue topology in embryonic epithelia.

Measurements on embryonic epithelial tissues in a diverse range of organisms have shown that the statistics of cell neighbor numbers are universal in tissues where cell proliferation is the primary cell activity. Highly simplified non-spatial models of proliferation are claimed to accurately reproduce these statistics. Using a systematic critical analysis, we show that non-spatial models are not capable of robustly describing the universal statistics observed in proliferating epithelia, indicating strong spatial correlations between cells.

Modeling gastrulation in the chick embryo: formation of the primitive streak.

The body plan of all higher organisms develops during gastrulation. Gastrulation results from the integration of cell proliferation, differentiation and migration of thousands of cells. In the chick embryo gastrulation starts with the formation of the primitive streak, the site of invagination of mesoderm and endoderm cells, from cells overlaying Koller's Sickle.

Who moves whom during primitive streak formation in the chick embryo.

Gastrulation is a critical stage in the development of all vertebrates. During gastrulation mesendoderm cells move inside the embryo to form the gut, muscles, and skeleton. In amniotes the mesendoderm cells move inside the embryo through a structure known as the primitive streak, extending from the posterior pole anterior through the midline of the embryo.

Imaging cell signalling and movement in development.

Imaging is a method of choice to investigate the complex spatio-temporal cellular dynamics and the signalling pathways that control them during development. The ability to tag many proteins in vivo makes it possible to analyse the detailed dynamics of these interactions ranging over several orders of magnitude; from the study of single molecule events on the millisecond and nanometre scale up to the complex three-dimensional behaviour of cells in tissues on the millimetre scale over time periods of hours to days. Great advances are being made in the detailed study of molecular processes using high resolution imaging techniques in transparent samples close to the surface of cells or tissues, where light scattering is minimal.

Collective cell migration in development.

Collective cell migration is a key process during the development of most organisms. It can involve either the migration of closely packed mesenchymal cells that make dynamic contacts with frequently changing neighbour cells, or the migration of epithelial sheets that typically display more stable cell-cell interactions and less frequent changes in neighbours. These collective movements can be controlled by short- or long-range dynamic gradients of extracellular signalling molecules, depending on the number of cells involved and their distance of migration.