@inbook{6178, abstract = {Mechanically coupled cells can generate forces driving cell and tissue morphogenesis during development. Visualization and measuring of these forces is of major importance to better understand the complexity of the biomechanic processes that shape cells and tissues. Here, we describe how UV laser ablation can be utilized to quantitatively assess mechanical tension in different tissues of the developing zebrafish and in cultures of primary germ layer progenitor cells ex vivo.}, author = {Smutny, Michael and Behrndt, Martin and Campinho, Pedro and Ruprecht, Verena and Heisenberg, Carl-Philipp J}, booktitle = {Tissue Morphogenesis}, editor = {Nelson, Celeste}, isbn = {9781493911639}, issn = {1940-6029}, pages = {219--235}, publisher = {Springer}, title = {{UV laser ablation to measure cell and tissue-generated forces in the zebrafish embryo in vivo and ex vivo}}, doi = {10.1007/978-1-4939-1164-6_15}, volume = {1189}, year = {2014}, } @article{1912, abstract = {Kupffer's vesicle (KV) is the zebrafish organ of laterality, patterning the embryo along its left-right (LR) axis. Regional differences in cell shape within the lumen-lining KV epithelium are essential for its LR patterning function. However, the processes by which KV cells acquire their characteristic shapes are largely unknown. Here, we show that the notochord induces regional differences in cell shape within KV by triggering extracellular matrix (ECM) accumulation adjacent to anterior-dorsal (AD) regions of KV. This localized ECM deposition restricts apical expansion of lumen-lining epithelial cells in AD regions of KV during lumen growth. Our study provides mechanistic insight into the processes by which KV translates global embryonic patterning into regional cell shape differences required for its LR symmetry-breaking function.}, author = {Compagnon, Julien and Barone, Vanessa and Rajshekar, Srivarsha and Kottmeier, Rita and Pranjic-Ferscha, Kornelija and Behrndt, Martin and Heisenberg, Carl-Philipp J}, journal = {Developmental Cell}, number = {6}, pages = {774 -- 783}, publisher = {Cell Press}, title = {{The notochord breaks bilateral symmetry by controlling cell shapes in the Zebrafish laterality organ}}, doi = {10.1016/j.devcel.2014.11.003}, volume = {31}, year = {2014}, } @phdthesis{1403, abstract = {A variety of developmental and disease related processes depend on epithelial cell sheet spreading. In order to gain insight into the biophysical mechanism(s) underlying the tissue morphogenesis we studied the spreading of an epithelium during the early development of the zebrafish embryo. In zebrafish epiboly the enveloping cell layer (EVL), a simple squamous epithelium, spreads over the yolk cell to completely engulf it at the end of gastrulation. Previous studies have proposed that an actomyosin ring forming within the yolk syncytial layer (YSL) acts as purse string that through constriction along its circumference pulls on the margin of the EVL. Direct biophysical evidence for this hypothesis has however been missing. The aim of the thesis was to understand how the actomyosin ring may generate pulling forces onto the EVL and what cellular mechanism(s) may facilitate the spreading of the epithelium. Using laser ablation to measure cortical tension within the actomyosin ring we found an anisotropic tension distribution, which was highest along the circumference of the ring. However the low degree of anisotropy was incompatible with the actomyosin ring functioning as a purse string only. Additionally, we observed retrograde cortical flow from vegetal parts of the ring into the EVL margin. Interpreting the experimental data using a theoretical distribution that models the tissues as active viscous gels led us to proposen that the actomyosin ring has a twofold contribution to EVL epiboly. It not only acts as a purse string through constriction along its circumference, but in addition constriction along the width of the ring generates pulling forces through friction-resisted cortical flow. Moreover, when rendering the purse string mechanism unproductive EVL epiboly proceeded normally indicating that the flow-friction mechanism is sufficient to drive the process. Aiming to understand what cellular mechanism(s) may facilitate the spreading of the epithelium we found that tension-oriented EVL cell divisions limit tissue anisotropy by releasing tension along the division axis and promote epithelial spreading. Notably, EVL cells undergo ectopic cell fusion in conditions in which oriented-cell division is impaired or the epithelium is mechanically challenged. Taken together our study of EVL epiboly suggests a novel mechanism of force generation for actomyosin rings through friction-resisted cortical flow and highlights the importance of tension-oriented cell divisions in epithelial morphogenesis.}, author = {Behrndt, Martin}, pages = {91}, publisher = {IST Austria}, title = {{Forces driving epithelial spreading in zebrafish epiboly}}, year = {2014}, } @article{2278, abstract = {It is firmly established that interactions between neurons and glia are fundamental across species for the correct establishment of a functional brain. Here, we found that the glia of the Drosophila larval brain display an essential non-autonomous role during the development of the optic lobe. The optic lobe develops from neuroepithelial cells that proliferate by dividing symmetrically until they switch to asymmetric/differentiative divisions that generate neuroblasts. The proneural gene lethal of scute (l9sc) is transiently activated by the epidermal growth factor receptor (EGFR)-Ras signal transduction pathway at the leading edge of a proneural wave that sweeps from medial to lateral neuroepithelium, promoting this switch. This process is tightly regulated by the tissue-autonomous function within the neuroepithelium of multiple signaling pathways, including EGFR-Ras and Notch. This study shows that the Notch ligand Serrate (Ser) is expressed in the glia and it forms a complex in vivo with Notch and Canoe, which colocalize at the adherens junctions of neuroepithelial cells. This complex is crucial for interactions between glia and neuroepithelial cells during optic lobe development. Ser is tissue-autonomously required in the glia where it activates Notch to regulate its proliferation, and non-autonomously in the neuroepithelium where Ser induces Notch signaling to avoid the premature activation of the EGFR-Ras pathway and hence of L9sc. Interestingly, different Notch activity reporters showed very different expression patterns in the glia and in the neuroepithelium, suggesting the existence of tissue-specific factors that promote the expression of particular Notch target genes or/and a reporter response dependent on different thresholds of Notch signaling.}, author = {Pérez Gómez, Raquel and Slovakova, Jana and Rives Quinto, Noemí and Krejčí, Alena and Carmena, Ana}, journal = {Journal of Cell Science}, number = {21}, pages = {4873 -- 4884}, publisher = {Company of Biologists}, title = {{A serrate-notch-canoe complex mediates essential interactions between glia and neuroepithelial cells during Drosophila optic lobe development}}, doi = {10.1242/jcs.125617}, volume = {126}, year = {2013}, } @article{2282, abstract = {Epithelial spreading is a common and fundamental aspect of various developmental and disease-related processes such as epithelial closure and wound healing. A key challenge for epithelial tissues undergoing spreading is to increase their surface area without disrupting epithelial integrity. Here we show that orienting cell divisions by tension constitutes an efficient mechanism by which the enveloping cell layer (EVL) releases anisotropic tension while undergoing spreading during zebrafish epiboly. The control of EVL cell-division orientation by tension involves cell elongation and requires myosin II activity to align the mitotic spindle with the main tension axis. We also found that in the absence of tension-oriented cell divisions and in the presence of increased tissue tension, EVL cells undergo ectopic fusions, suggesting that the reduction of tension anisotropy by oriented cell divisions is required to prevent EVL cells from fusing. We conclude that cell-division orientation by tension constitutes a key mechanism for limiting tension anisotropy and thus promoting tissue spreading during EVL epiboly.}, author = {Campinho, Pedro and Behrndt, Martin and Ranft, Jonas and Risler, Thomas and Minc, Nicolas and Heisenberg, Carl-Philipp J}, journal = {Nature Cell Biology}, pages = {1405 -- 1414}, publisher = {Nature Publishing Group}, title = {{Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly}}, doi = {10.1038/ncb2869}, volume = {15}, year = {2013}, } @article{2286, abstract = {The spatiotemporal control of cell divisions is a key factor in epithelial morphogenesis and patterning. Mao et al (2013) now describe how differential rates of proliferation within the Drosophila wing disc epithelium give rise to anisotropic tissue tension in peripheral/proximal regions of the disc. Such global tissue tension anisotropy in turn determines the orientation of cell divisions by controlling epithelial cell elongation.}, author = {Campinho, Pedro and Heisenberg, Carl-Philipp J}, journal = {EMBO Journal}, number = {21}, pages = {2783 -- 2784}, publisher = {Wiley-Blackwell}, title = {{The force and effect of cell proliferation}}, doi = {10.1038/emboj.2013.225}, volume = {32}, year = {2013}, } @article{2469, abstract = {Cadherins are transmembrane proteins that mediate cell–cell adhesion in animals. By regulating contact formation and stability, cadherins play a crucial role in tissue morphogenesis and homeostasis. Here, we review the three major unctions of cadherins in cell–cell contact formation and stability. Two of those functions lead to a decrease in interfacial ension at the forming cell–cell contact, thereby promoting contact expansion — first, by providing adhesion tension that lowers interfacial tension at the cell–cell contact, and second, by signaling to the actomyosin cytoskeleton in order to reduce cortex tension and thus interfacial tension at the contact. The third function of cadherins in cell–cell contact formation is to stabilize the contact by resisting mechanical forces that pull on the contact.}, author = {Maître, Jean-Léon and Heisenberg, Carl-Philipp J}, journal = {Current Biology}, number = {14}, pages = {R626 -- R633}, publisher = {Cell Press}, title = {{Three functions of cadherins in cell adhesion}}, doi = {10.1016/j.cub.2013.06.019}, volume = {23}, year = {2013}, } @article{2833, abstract = {During development, mechanical forces cause changes in size, shape, number, position, and gene expression of cells. They are therefore integral to any morphogenetic processes. Force generation by actin-myosin networks and force transmission through adhesive complexes are two self-organizing phenomena driving tissue morphogenesis. Coordination and integration of forces by long-range force transmission and mechanosensing of cells within tissues produce large-scale tissue shape changes. Extrinsic mechanical forces also control tissue patterning by modulating cell fate specification and differentiation. Thus, the interplay between tissue mechanics and biochemical signaling orchestrates tissue morphogenesis and patterning in development.}, author = {Heisenberg, Carl-Philipp J and Bellaïche, Yohanns}, journal = {Cell}, number = {5}, pages = {948 -- 962}, publisher = {Cell Press}, title = {{Forces in tissue morphogenesis and patterning}}, doi = {10.1016/j.cell.2013.05.008}, volume = {153}, year = {2013}, } @article{2841, abstract = {In zebrafish early development, blastoderm cells undergo extensive radial intercalations, triggering the spreading of the blastoderm over the yolk cell and thereby initiating embryonic body axis formation. Now reporting in Developmental Cell, Song et al. (2013) demonstrate a critical function for EGF-dependent E-cadherin endocytosis in promoting blastoderm cell intercalations.}, author = {Morita, Hitoshi and Heisenberg, Carl-Philipp J}, journal = {Developmental Cell}, number = {6}, pages = {567 -- 569}, publisher = {Cell Press}, title = {{Holding on and letting go: Cadherin turnover in cell intercalation}}, doi = {10.1016/j.devcel.2013.03.007}, volume = {24}, year = {2013}, } @article{2862, abstract = {Motile cilia perform crucial functions during embryonic development and throughout adult life. Development of organs containing motile cilia involves regulation of cilia formation (ciliogenesis) and formation of a luminal space (lumenogenesis) in which cilia generate fluid flows. Control of ciliogenesis and lumenogenesis is not yet fully understood, and it remains unclear whether these processes are coupled. In the zebrafish embryo, lethal giant larvae 2 (lgl2) is expressed prominently in ciliated organs. Lgl proteins are involved in establishing cell polarity and have been implicated in vesicle trafficking. Here, we identified a role for Lgl2 in development of ciliated epithelia in Kupffer's vesicle, which directs left-right asymmetry of the embryo; the otic vesicles, which give rise to the inner ear; and the pronephric ducts of the kidney. Using Kupffer's vesicle as a model ciliated organ, we found that depletion of Lgl2 disrupted lumen formation and reduced cilia number and length. Immunofluorescence and time-lapse imaging of Kupffer's vesicle morphogenesis in Lgl2-deficient embryos suggested cell adhesion defects and revealed loss of the adherens junction component E-cadherin at lateral membranes. Genetic interaction experiments indicate that Lgl2 interacts with Rab11a to regulate E-cadherin and mediate lumen formation that is uncoupled from cilia formation. These results uncover new roles and interactions for Lgl2 that are crucial for both lumenogenesis and ciliogenesis and indicate that these processes are genetically separable in zebrafish.}, author = {Tay, Hwee and Schulze, Sabrina and Compagnon, Julien and Foley, Fiona and Heisenberg, Carl-Philipp J and Yost, H Joseph and Abdelilah Seyfried, Salim and Amack, Jeffrey}, journal = {Development}, number = {7}, pages = {1550 -- 1559}, publisher = {Company of Biologists}, title = {{Lethal giant larvae 2 regulates development of the ciliated organ Kupffer’s vesicle}}, doi = {10.1242/dev.087130}, volume = {140}, year = {2013}, } @article{2884, author = {Maître, Jean-Léon and Berthoumieux, Hélène and Krens, Gabriel and Salbreux, Guillaume and Julicher, Frank and Paluch, Ewa and Heisenberg, Carl-Philipp J}, journal = {Medecine Sciences}, number = {2}, pages = {147 -- 150}, publisher = {Éditions Médicales et Scientifiques}, title = {{Cell adhesion mechanics of zebrafish gastrulation}}, doi = {10.1051/medsci/2013292011}, volume = {29}, year = {2013}, } @article{2918, abstract = {Oriented mitosis is essential during tissue morphogenesis. The Wnt/planar cell polarity (Wnt/PCP) pathway orients mitosis in a number of developmental systems, including dorsal epiblast cell divisions along the animal-vegetal (A-V) axis during zebrafish gastrulation. How Wnt signalling orients the mitotic plane is, however, unknown. Here we show that, in dorsal epiblast cells, anthrax toxin receptor 2a (Antxr2a) accumulates in a polarized cortical cap, which is aligned with the embryonic A-V axis and forecasts the division plane. Filamentous actin (F-actin) also forms an A-V polarized cap, which depends on Wnt/PCP and its effectors RhoA and Rock2. Antxr2a is recruited to the cap by interacting with actin. Antxr2a also interacts with RhoA and together they activate the diaphanous-related formin zDia2. Mechanistically, Antxr2a functions as a Wnt-dependent polarized determinant, which, through the action of RhoA and zDia2, exerts torque on the spindle to align it with the A-V axis. }, author = {Castanon, Irinka and Abrami, Laurence and Holtzer, Laurent and Heisenberg, Carl-Philipp J and Van Der Goot, Françoise and González Gaitán, Marcos}, journal = {Nature Cell Biology}, number = {1}, pages = {28 -- 39}, publisher = {Nature Publishing Group}, title = {{Anthrax toxin receptor 2a controls mitotic spindle positioning}}, doi = {10.1038/ncb2632}, volume = {15}, year = {2013}, } @article{2920, abstract = {Cell polarisation in development is a common and fundamental process underlying embryo patterning and morphogenesis, and has been extensively studied over the past years. Our current knowledge of cell polarisation in development is predominantly based on studies that have analysed polarisation of single cells, such as eggs, or cellular aggregates with a stable polarising interface, such as cultured epithelial cells (St Johnston and Ahringer, 2010). However, in embryonic development, particularly of vertebrates, cell polarisation processes often encompass large numbers of cells that are placed within moving and proliferating tissues, and undergo mesenchymal-to-epithelial transitions with a highly complex spatiotemporal choreography. How such intricate cell polarisation processes in embryonic development are achieved has only started to be analysed. By using live imaging of neurulation in the transparent zebrafish embryo, Buckley et al (2012) now describe a novel polarisation strategy by which cells assemble an apical domain in the part of their cell body that intersects with the midline of the forming neural rod. This mechanism, along with the previously described mirror-symmetric divisions (Tawk et al, 2007), is thought to trigger formation of both neural rod midline and lumen.}, author = {Compagnon, Julien and Heisenberg, Carl-Philipp J}, journal = {EMBO Journal}, number = {1}, pages = {1 -- 3}, publisher = {Wiley-Blackwell}, title = {{Neurulation coordinating cell polarisation and lumen formation}}, doi = {10.1038/emboj.2012.325}, volume = {32}, year = {2013}, } @phdthesis{1406, abstract = {Epithelial spreading is a critical part of various developmental and wound repair processes. Here we use zebrafish epiboly as a model system to study the cellular and molecular mechanisms underlying the spreading of epithelial sheets. During zebrafish epiboly the enveloping cell layer (EVL), a simple squamous epithelium, spreads over the embryo to eventually cover the entire yolk cell by the end of gastrulation. The EVL leading edge is anchored through tight junctions to the yolk syncytial layer (YSL), where directly adjacent to the EVL margin a contractile actomyosin ring is formed that is thought to drive EVL epiboly. The prevalent view in the field was that the contractile ring exerts a pulling force on the EVL margin, which pulls the EVL towards the vegetal pole. However, how this force is generated and how it affects EVL morphology still remains elusive. Moreover, the cellular mechanisms mediating the increase in EVL surface area, while maintaining tissue integrity and function are still unclear. Here we show that the YSL actomyosin ring pulls on the EVL margin by two distinct force-generating mechanisms. One mechanism is based on contraction of the ring around its circumference, as previously proposed. The second mechanism is based on actomyosin retrogade flows, generating force through resistance against the substrate. The latter can function at any epiboly stage even in situations where the contraction-based mechanism is unproductive. Additionally, we demonstrate that during epiboly the EVL is subjected to anisotropic tension, which guides the orientation of EVL cell division along the main axis (animal-vegetal) of tension. The influence of tension in cell division orientation involves cell elongation and requires myosin-2 activity for proper spindle alignment. Strikingly, we reveal that tension-oriented cell divisions release anisotropic tension within the EVL and that in the absence of such divisions, EVL cells undergo ectopic fusions. We conclude that forces applied to the EVL by the action of the YSL actomyosin ring generate a tension anisotropy in the EVL that orients cell divisions, which in turn limit tissue tension increase thereby facilitating tissue spreading.}, author = {Campinho, Pedro}, issn = {2663-337X}, pages = {123}, publisher = {Institute of Science and Technology Austria}, title = {{Mechanics of zebrafish epiboly: Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading}}, year = {2013}, } @article{2926, abstract = {To fight infectious diseases, host immune defenses are employed at multiple levels. Sanitary behavior, such as pathogen avoidance and removal, acts as a first line of defense to prevent infection [1] before activation of the physiological immune system. Insect societies have evolved a wide range of collective hygiene measures and intensive health care toward pathogen-exposed group members [2]. One of the most common behaviors is allogrooming, in which nestmates remove infectious particles from the body surfaces of exposed individuals [3]. Here we show that, in invasive garden ants, grooming of fungus-exposed brood is effective beyond the sheer mechanical removal of fungal conidiospores; it also includes chemical disinfection through the application of poison produced by the ants themselves. Formic acid is the main active component of the poison. It inhibits fungal growth of conidiospores remaining on the brood surface after grooming and also those collected in the mouth of the grooming ant. This dual function is achieved by uptake of the poison droplet into the mouth through acidopore self-grooming and subsequent application onto the infectious brood via brood grooming. This extraordinary behavior extends the current understanding of grooming and the establishment of social immunity in insect societies.}, author = {Tragust, Simon and Mitteregger, Barbara and Barone, Vanessa and Konrad, Matthias and Ugelvig, Line V and Cremer, Sylvia}, journal = {Current Biology}, number = {1}, pages = {76 -- 82}, publisher = {Cell Press}, title = {{Ants disinfect fungus-exposed brood by oral uptake and spread of their poison}}, doi = {10.1016/j.cub.2012.11.034}, volume = {23}, year = {2013}, } @article{2950, abstract = {Contractile actomyosin rings drive various fundamental morphogenetic processes ranging from cytokinesis to wound healing. Actomyosin rings are generally thought to function by circumferential contraction. Here, we show that the spreading of the enveloping cell layer (EVL) over the yolk cell during zebrafish gastrulation is driven by a contractile actomyosin ring. In contrast to previous suggestions, we find that this ring functions not only by circumferential contraction but also by a flow-friction mechanism. This generates a pulling force through resistance against retrograde actomyosin flow. EVL spreading proceeds normally in situations where circumferential contraction is unproductive, indicating that the flow-friction mechanism is sufficient. Thus, actomyosin rings can function in epithelial morphogenesis through a combination of cable-constriction and flow-friction mechanisms.}, author = {Behrndt, Martin and Salbreux, Guillaume and Campinho, Pedro and Hauschild, Robert and Oswald, Felix and Roensch, Julia and Grill, Stephan and Heisenberg, Carl-Philipp J}, journal = {Science}, number = {6104}, pages = {257 -- 260}, publisher = {American Association for the Advancement of Science}, title = {{Forces driving epithelial spreading in zebrafish gastrulation}}, doi = {10.1126/science.1224143}, volume = {338}, year = {2012}, } @article{2951, abstract = {Differential cell adhesion and cortex tension are thought to drive cell sorting by controlling cell-cell contact formation. Here, we show that cell adhesion and cortex tension have different mechanical functions in controlling progenitor cell-cell contact formation and sorting during zebrafish gastrulation. Cortex tension controls cell-cell contact expansion by modulating interfacial tension at the contact. By contrast, adhesion has little direct function in contact expansion, but instead is needed to mechanically couple the cortices of adhering cells at their contacts, allowing cortex tension to control contact expansion. The coupling function of adhesion is mediated by E-cadherin and limited by the mechanical anchoring of E-cadherin to the cortex. Thus, cell adhesion provides the mechanical scaffold for cell cortex tension to drive cell sorting during gastrulation.}, author = {Maître, Jean-Léon and Berthoumieux, Hélène and Krens, Gabriel and Salbreux, Guillaume and Julicher, Frank and Paluch, Ewa and Heisenberg, Carl-Philipp J}, journal = {Science}, number = {6104}, pages = {253 -- 256}, publisher = {American Association for the Advancement of Science}, title = {{Adhesion functions in cell sorting by mechanically coupling the cortices of adhering cells}}, doi = {10.1126/science.1225399}, volume = {338}, year = {2012}, } @article{2952, abstract = {Body axis elongation represents a common and fundamental morphogenetic process in development. A key mechanism triggering body axis elongation without additional growth is convergent extension (CE), whereby a tissue undergoes simultaneous narrowing and extension. Both collective cell migration and cell intercalation are thought to drive CE and are used to different degrees in various species as they elongate their body axis. Here, we provide an overview of CE as a general strategy for body axis elongation and discuss conserved and divergent mechanisms underlying CE among different species.}, author = {Tada, Masazumi and Heisenberg, Carl-Philipp J}, journal = {Development}, number = {21}, pages = {3897 -- 3904}, publisher = {Company of Biologists}, title = {{Convergent extension Using collective cell migration and cell intercalation to shape embryos}}, doi = {10.1242/dev.073007}, volume = {139}, year = {2012}, } @article{2953, author = {Heisenberg, Carl-Philipp J and Fässler, Reinhard}, journal = {Current Opinion in Cell Biology}, number = {5}, pages = {559 -- 561}, publisher = {Elsevier}, title = {{Cell-cell adhesion and extracellular matrix diversity counts}}, doi = {10.1016/j.ceb.2012.09.002}, volume = {24}, year = {2012}, } @article{3245, abstract = {How cells orchestrate their behavior during collective migration is a long-standing question. Using magnetic tweezers to apply mechanical stimuli to Xenopus mesendoderm cells, Weber etal. (2012) now reveal, in this issue of Developmental Cell, a cadherin-mediated mechanosensitive response that promotes cell polarization and movement persistence during the collective mesendoderm migration in gastrulation.}, author = {Behrndt, Martin and Heisenberg, Carl-Philipp J}, journal = {Developmental Cell}, number = {1}, pages = {3 -- 4}, publisher = {Cell Press}, title = {{Spurred by resistance mechanosensation in collective migration}}, doi = {10.1016/j.devcel.2011.12.018}, volume = {22}, year = {2012}, } @article{3246, abstract = {Visualizing and analyzing shape changes at various scales, ranging from single molecules to whole organisms, are essential for understanding complex morphogenetic processes, such as early embryonic development. Embryo morphogenesis relies on the interplay between different tissues, the properties of which are again determined by the interaction between their constituent cells. Cell interactions, on the other hand, are controlled by various molecules, such as signaling and adhesion molecules, which in order to exert their functions need to be spatiotemporally organized within and between the interacting cells. In this review, we will focus on the role of cell adhesion functioning at different scales to organize cell, tissue and embryo morphogenesis. We will specifically ask how the subcellular distribution of adhesion molecules controls the formation of cell-cell contacts, how cell-cell contacts determine tissue shape, and how tissue interactions regulate embryo morphogenesis.}, author = {Barone, Vanessa and Heisenberg, Carl-Philipp J}, journal = {Current Opinion in Cell Biology}, number = {1}, pages = {148 -- 153}, publisher = {Elsevier}, title = {{Cell adhesion in embryo morphogenesis}}, doi = {10.1016/j.ceb.2011.11.006}, volume = {24}, year = {2012}, } @article{3288, abstract = {The zonula adherens (ZA) of epithelial cells is a site of cell-cell adhesion where cellular forces are exerted and resisted. Increasing evidence indicates that E-cadherin adhesion molecules at the ZA serve to sense force applied on the junctions and coordinate cytoskeletal responses to those forces. Efforts to understand the role that cadherins play in mechanotransduction have been limited by the lack of assays to measure the impact of forces on the ZA. In this study we used 4D imaging of GFP-tagged E-cadherin to analyse the movement of the ZA. Junctions in confluent epithelial monolayers displayed prominent movements oriented orthogonal (perpendicular) to the ZA itself. Two components were identified in these movements: a relatively slow unidirectional (translational) component that could be readily fitted by least-squares regression analysis, upon which were superimposed more rapid oscillatory movements. Myosin IIB was a dominant factor responsible for driving the unilateral translational movements. In contrast, frequency spectrum analysis revealed that depletion of Myosin IIA increased the power of the oscillatory movements. This implies that Myosin IIA may serve to dampen oscillatory movements of the ZA. This extends our recent analysis of Myosin II at the ZA to demonstrate that Myosin IIA and Myosin IIB make distinct contributions to junctional movement at the ZA.}, author = {Smutny, Michael and Wu, Selwin and Gomez, Guillermo and Mangold, Sabine and Yap, Alpha and Hamilton, Nicholas}, journal = {PLoS One}, number = {7}, publisher = {Public Library of Science}, title = {{Multicomponent analysis of junctional movements regulated by Myosin II isoforms at the epithelial zonula adherens}}, doi = {10.1371/journal.pone.0022458}, volume = {6}, year = {2011}, } @article{3287, abstract = {Diffusing membrane constituents are constantly exposed to a variety of forces that influence their stochastic path. Single molecule experiments allow for resolving trajectories at extremely high spatial and temporal accuracy, thereby offering insights into en route interactions of the tracer. In this review we discuss approaches to derive information about the underlying processes, based on single molecule tracking experiments. In particular, we focus on a new versatile way to analyze single molecule diffusion in the absence of a full analytical treatment. The method is based on comprehensive comparison of an experimental data set against the hypothetical outcome of multiple experiments performed on the computer. Since Monte Carlo simulations can be easily and rapidly performed even on state-of-the-art PCs, our method provides a simple way for testing various - even complicated - diffusion models. We describe the new method in detail, and show the applicability on two specific examples: firstly, kinetic rate constants can be derived for the transient interaction of mobile membrane proteins; secondly, residence time and corral size can be extracted for confined diffusion.}, author = {Ruprecht, Verena and Axmann, Markus and Wieser, Stefan and Schuetz, Gerhard}, journal = {Current Protein & Peptide Science}, number = {8}, pages = {714 -- 724}, publisher = {Bentham Science Publishers}, title = {{What can we learn from single molecule trajectories?}}, doi = {10.2174/138920311798841753}, volume = {12}, year = {2011}, } @article{3368, abstract = {Tissue surface tension (TST) is an important mechanical property influencing cell sorting and tissue envelopment. The study by Manning et al. (1) reported on a mathematical model describing TST on the basis of the balance between adhesive and tensile properties of the constituent cells. The model predicts that, in high-adhesion cell aggregates, surface cells will be stretched to maintain the same area of cell–cell contact as interior bulk cells, resulting in an elongated and flattened cell shape. The authors (1) observed flat and elongated cells at the surface of high-adhesion zebrafish germ-layer explants, which they argue are undifferentiated stretched germ-layer progenitor cells, and they use this observation as a validation of their model.}, author = {Krens, Gabriel and Möllmert, Stephanie and Heisenberg, Carl-Philipp J}, journal = {PNAS}, number = {3}, pages = {E9 -- E10}, publisher = {National Academy of Sciences}, title = {{Enveloping cell layer differentiation at the surface of zebrafish germ layer tissue explants}}, doi = {10.1073/pnas.1010767108}, volume = {108}, year = {2011}, } @article{3396, abstract = {Facial branchiomotor neurons (FBMNs) in zebrafish and mouse embryonic hindbrain undergo a characteristic tangential migration from rhombomere (r) 4, where they are born, to r6/7. Cohesion among neuroepithelial cells (NCs) has been suggested to function in FBMN migration by inhibiting FBMNs positioned in the basal neuroepithelium such that they move apically between NCs towards the midline of the neuroepithelium instead of tangentially along the basal side of the neuroepithelium towards r6/7. However, direct experimental evaluation of this hypothesis is still lacking. Here, we have used a combination of biophysical cell adhesion measurements and high-resolution time-lapse microscopy to determine the role of NC cohesion in FBMN migration. We show that reducing NC cohesion by interfering with Cadherin 2 (Cdh2) activity results in FBMNs positioned at the basal side of the neuroepithelium moving apically towards the neural tube midline instead of tangentially towards r6/7. In embryos with strongly reduced NC cohesion, ectopic apical FBMN movement frequently results in fusion of the bilateral FBMN clusters over the apical midline of the neural tube. By contrast, reducing cohesion among FBMNs by interfering with Contactin 2 (Cntn2) expression in these cells has little effect on apical FBMN movement, but reduces the fusion of the bilateral FBMN clusters in embryos with strongly diminished NC cohesion. These data provide direct experimental evidence that NC cohesion functions in tangential FBMN migration by restricting their apical movement.}, author = {Stockinger, Petra and Heisenberg, Carl-Philipp J and Maître, Jean-Léon}, journal = {Development}, number = {21}, pages = {4673 -- 4683}, publisher = {Company of Biologists}, title = {{Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron migration in the zebrafish neural tube}}, doi = {10.1242/dev.071233}, volume = {138}, year = {2011}, } @article{3397, abstract = {Recent advances in microscopy techniques and biophysical measurements have provided novel insight into the molecular, cellular and biophysical basis of cell adhesion. However, comparably little is known about a core element of cell–cell adhesion—the energy of adhesion at the cell–cell contact. In this review, we discuss approaches to understand the nature and regulation of adhesion energy, and propose strategies to determine adhesion energy between cells in vitro and in vivo.}, author = {Maître, Jean-Léon and Heisenberg, Carl-Philipp J}, journal = {Current Opinion in Cell Biology}, number = {5}, pages = {508 -- 514}, publisher = {Elsevier}, title = {{The role of adhesion energy in controlling cell-cell contacts}}, doi = {10.1016/j.ceb.2011.07.004}, volume = {23}, year = {2011}, } @article{3379, abstract = {The process of gastrulation is highly conserved across vertebrates on both the genetic and morphological levels, despite great variety in embryonic shape and speed of development. This mechanism spatially separates the germ layers and establishes the organizational foundation for future development. Mesodermal identity is specified in a superficial layer of cells, the epiblast, where cells maintain an epithelioid morphology. These cells involute to join the deeper hypoblast layer where they adopt a migratory, mesenchymal morphology. Expression of a cascade of related transcription factors orchestrates the parallel genetic transition from primitive to mature mesoderm. Although the early and late stages of this process are increasingly well understood, the transition between them has remained largely mysterious. We present here the first high resolution in vivo observations of the blebby transitional morphology of involuting mesodermal cells in a vertebrate embryo. We further demonstrate that the zebrafish spadetail mutation creates a reversible block in the maturation program, stalling cells in the transition state. This mutation creates an ideal system for dissecting the specific properties of cells undergoing the morphological transition of maturing mesoderm, as we demonstrate with a direct measurement of cell–cell adhesion.}, author = {Row, Richard and Maître, Jean-Léon and Martin, Benjamin and Stockinger, Petra and Heisenberg, Carl-Philipp J and Kimelman, David}, journal = {Developmental Biology}, number = {1}, pages = {102 -- 110}, publisher = {Elsevier}, title = {{Completion of the epithelial to mesenchymal transition in zebrafish mesoderm requires Spadetail}}, doi = {10.1016/j.ydbio.2011.03.025}, volume = {354}, year = {2011}, } @article{3383, author = {Heisenberg, Carl-Philipp J}, journal = {FEBS Journal}, number = {S1}, pages = {24 -- 24}, publisher = {Wiley-Blackwell}, title = {{Invited Lectures ‐ Symposia Area}}, doi = {10.1111/j.1742-4658.2011.08136.x}, volume = {278}, year = {2011}, } @inbook{3791, abstract = {During the development of multicellular organisms, cell fate specification is followed by the sorting of different cell types into distinct domains from where the different tissues and organs are formed. Cell sorting involves both the segregation of a mixed population of cells with different fates and properties into distinct domains, and the active maintenance of their segregated state. Because of its biological importance and apparent resemblance to fluid segregation in physics, cell sorting was extensively studied by both biologists and physicists over the last decades. Different theories were developed that try to explain cell sorting on the basis of the physical properties of the constituent cells. However, only recently the molecular and cellular mechanisms that control the physical properties driving cell sorting, have begun to be unraveled. In this review, we will provide an overview of different cell-sorting processes in development and discuss how these processes can be explained by the different sorting theories, and how these theories in turn can be connected to the molecular and cellular mechanisms driving these processes.}, author = {Krens, Gabriel and Heisenberg, Carl-Philipp J}, booktitle = {Forces and Tension in Development}, editor = {Labouesse, Michel}, pages = {189 -- 213}, publisher = {Elsevier}, title = {{Cell sorting in development}}, doi = {10.1016/B978-0-12-385065-2.00006-2}, volume = {95}, year = {2011}, } @phdthesis{3273, author = {Maître, Jean-Léon}, issn = {2663-337X}, publisher = {Institute of Science and Technology Austria}, title = {{Mechanics of adhesion and de‐adhesion in zebrafish germ layer progenitors}}, year = {2011}, } @article{3373, abstract = {The use of optical traps to measure or apply forces on the molecular level requires a precise knowledge of the trapping force field. Close to the trap center, this field is typically approximated as linear in the displacement of the trapped microsphere. However, applications demanding high forces at low laser intensities can probe the light-microsphere interaction beyond the linear regime. Here, we measured the full nonlinear force and displacement response of an optical trap in two dimensions using a dual-beam optical trap setup with back-focal-plane photodetection. We observed a substantial stiffening of the trap beyond the linear regime that depends on microsphere size, in agreement with Mie theory calculations. Surprisingly, we found that the linear detection range for forces exceeds the one for displacement by far. Our approach allows for a complete calibration of an optical trap.}, author = {Jahnel, Marcus and Behrndt, Martin and Jannasch, Anita and Schaeffer, Erik and Grill, Stephan}, journal = {Optics Letters}, number = {7}, pages = {1260 -- 1262}, publisher = {Optica Publishing Group}, title = {{Measuring the complete force field of an optical trap}}, doi = {10.1364/OL.36.001260}, volume = {36}, year = {2011}, } @article{3790, abstract = {Cell shape and motility are primarily controlled by cellular mechanics. The attachment of the plasma membrane to the underlying actomyosin cortex has been proposed to be important for cellular processes involving membrane deformation. However, little is known about the actual function of membrane-to-cortex attachment (MCA) in cell protrusion formation and migration, in particular in the context of the developing embryo. Here, we use a multidisciplinary approach to study MCA in zebrafish mesoderm and endoderm (mesendoderm) germ layer progenitor cells, which migrate using a combination of different protrusion types, namely, lamellipodia, filopodia, and blebs, during zebrafish gastrulation. By interfering with the activity of molecules linking the cortex to the membrane and measuring resulting changes in MCA by atomic force microscopy, we show that reducing MCA in mesendoderm progenitors increases the proportion of cellular blebs and reduces the directionality of cell migration. We propose that MCA is a key parameter controlling the relative proportions of different cell protrusion types in mesendoderm progenitors, and thus is key in controlling directed migration during gastrulation.}, author = {Diz Muñoz, Alba and Krieg, Michael and Bergert, Martin and Ibarlucea Benitez, Itziar and Müller, Daniel and Paluch, Ewa and Heisenberg, Carl-Philipp J}, journal = {PLoS Biology}, number = {11}, publisher = {Public Library of Science}, title = {{Control of directed cell migration in vivo by membrane-to-cortex attachment}}, doi = {10.1371/journal.pbio.1000544}, volume = {8}, year = {2010}, } @article{3789, abstract = {The development of multicellular organisms is dependent on the tight coordination between tissue growth and morphogenesis. The stereotypical orientation of cell divisions has been proposed to be a fundamental mechanism by which proliferating and growing tissues take shape. However, the actual contribution of stereotypical division orientation (SDO) to tissue morphogenesis is unclear. In zebrafish, cell divisions with stereotypical orientation have been implicated in both body-axis elongation and neural rod formation [1, 2], although there is little direct evidence for a critical function of SDO in either of these processes. Here we show that SDO is required for formation of the neural rod midline during neurulation but dispensable for elongation of the body axis during gastrulation. Our data indicate that SDO during both gastrulation and neurulation is dependent on the noncanonical Wnt receptor Frizzled 7 (Fz7) and that interfering with cell division orientation leads to severe defects in neural rod midline formation but not body-axis elongation. These findings suggest a novel function for Fz7-controlled cell division orientation in neural rod midline formation during neurulation. }, author = {Quesada-Hernández, Elena and Caneparo, Luca and Schneider, Sylvia and Winkler, Sylke and Liebling, Michael and Fraser, Scott and Heisenberg, Carl-Philipp J}, journal = {Current Biology}, number = {21}, pages = {1966 -- 1972}, publisher = {Cell Press}, title = {{Stereotypical cell division orientation controls neural rod midline formation in zebrafish}}, doi = {10.1016/j.cub.2010.10.009}, volume = {20}, year = {2010}, } @article{3788, abstract = {Cell sorting is a widespread phenomenon pivotal to the early development of multicellular organisms. In vitro cell sorting studies have been instrumental in revealing the cellular properties driving this process. However, these studies have as yet been limited to two-dimensional analysis of three-dimensional cell sorting events. Here we describe a method to record the sorting of primary zebrafish ectoderm and mesoderm germ layer progenitor cells in three dimensions over time, and quantitatively analyze their sorting behavior using an order parameter related to heterotypic interface length. We investigate the cell population size dependence of sorted aggregates and find that the germ layer progenitor cells engulfed in the final configuration display a relationship between total interfacial length and system size according to a simple geometrical argument, subject to a finite-size effect.}, author = {Klopper, Abigail and Krens, Gabriel and Grill, Stephan and Heisenberg, Carl-Philipp J}, journal = {The European Physical Journal E: Soft Matter and Biological Physics}, number = {2}, pages = {99 -- 103}, publisher = {Springer}, title = {{Finite-size corrections to scaling behavior in sorted cell aggregates}}, doi = {10.1140/epje/i2010-10642-y}, volume = {33}, year = {2010}, } @article{4157, abstract = {Integrin- and cadherin-mediated adhesion is central for cell and tissue morphogenesis, allowing cells and tissues to change shape without loosing integrity. Studies predominantly in cell culture showed that mechanosensation through adhesion structures is achieved by force-mediated modulation of their molecular composition. The specific molecular composition of adhesion sites in turn determines their signalling activity and dynamic reorganization. Here, we will review how adhesion sites respond to mecanical stimuli, and how spatially and temporally regulated signalling from different adhesion sites controls cell migration and tissue morphogenesis.}, author = {Papusheva, Ekaterina and Heisenberg, Carl-Philipp J}, journal = {EMBO Journal}, number = {16}, pages = {2753 -- 2768}, publisher = {Wiley-Blackwell}, title = {{Spatial organization of adhesion: force-dependent regulation and function in tissue morphogenesis}}, doi = {10.1038/emboj.2010.182}, volume = {29}, year = {2010}, } @phdthesis{3962, author = {Pflicke, Holger}, issn = {2663-337X}, publisher = {Institute of Science and Technology Austria}, title = {{Dendritic cell migration across basement membranes in the skin}}, year = {2010}, }