TY - JOUR AB - The formation of self-organized patterns is key to the morphogenesis of multicellular organisms, although a comprehensive theory of biological pattern formation is still lacking. Here, we propose a minimal model combining tissue mechanics with morphogen turnover and transport to explore routes to patterning. Our active description couples morphogen reaction and diffusion, which impact cell differentiation and tissue mechanics, to a two-phase poroelastic rheology, where one tissue phase consists of a poroelastic cell network and the other one of a permeating extracellular fluid, which provides a feedback by actively transporting morphogens. While this model encompasses previous theories approximating tissues to inert monophasic media, such as Turing’s reaction–diffusion model, it overcomes some of their key limitations permitting pattern formation via any two-species biochemical kinetics due to mechanically induced cross-diffusion flows. Moreover, we describe a qualitatively different advection-driven Keller–Segel instability which allows for the formation of patterns with a single morphogen and whose fundamental mode pattern robustly scales with tissue size. We discuss the potential relevance of these findings for tissue morphogenesis. AU - Recho, Pierre AU - Hallou, Adrien AU - Hannezo, Edouard B ID - 6191 IS - 12 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 00278424 TI - Theory of mechanochemical patterning in biphasic biological tissues VL - 116 ER - TY - JOUR AB - Increased levels of the chemokine CCL2 in cancer patients are associated with poor prognosis. Experimental evidence suggests that CCL2 correlates with inflammatory monocyte recruitment and induction of vascular activation, but the functionality remains open. Here, we show that endothelial Ccr2 facilitates pulmonary metastasis using an endothelial-specific Ccr2-deficient mouse model (Ccr2ecKO). Similar levels of circulating monocytes and equal leukocyte recruitment to metastatic lesions of Ccr2ecKO and Ccr2fl/fl littermates were observed. The absence of endothelial Ccr2 strongly reduced pulmonary metastasis, while the primary tumor growth was unaffected. Despite a comparable cytokine milieu in Ccr2ecKO and Ccr2fl/fl littermates the absence of vascular permeability induction was observed only in Ccr2ecKO mice. CCL2 stimulation of pulmonary endothelial cells resulted in increased phosphorylation of MLC2, endothelial cell retraction, and vascular leakiness that was blocked by an addition of a CCR2 inhibitor. These data demonstrate that endothelial CCR2 expression is required for tumor cell extravasation and pulmonary metastasis. Implications: The findings provide mechanistic insight into how CCL2–CCR2 signaling in endothelial cells promotes their activation through myosin light chain phosphorylation, resulting in endothelial retraction and enhanced tumor cell migration and metastasis. AU - Roblek, Marko AU - Protsyuk, Darya AU - Becker, Paul F. AU - Stefanescu, Cristina AU - Gorzelanny, Christian AU - Glaus Garzon, Jesus F. AU - Knopfova, Lucia AU - Heikenwalder, Mathias AU - Luckow, Bruno AU - Schneider, Stefan W. AU - Borsig, Lubor ID - 6190 IS - 3 JF - Molecular Cancer Research SN - 15417786 TI - CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis VL - 17 ER - TY - JOUR AB - Great care is needed when interpreting claims about the genetic basis of human variation based on data from genome-wide association studies. AU - Barton, Nicholas H AU - Hermisson, Joachim AU - Nordborg, Magnus ID - 6230 JF - eLife TI - Why structure matters VL - 8 ER - TY - JOUR AB - The boundary behaviour of solutions of stochastic PDEs with Dirichlet boundary conditions can be surprisingly—and in a sense, arbitrarily—bad: as shown by Krylov[ SIAM J. Math. Anal.34(2003) 1167–1182], for any α>0 one can find a simple 1-dimensional constant coefficient linear equation whose solution at the boundary is not α-Hölder continuous.We obtain a positive counterpart of this: under some mild regularity assumptions on the coefficients, solutions of semilinear SPDEs on C1 domains are proved to be α-Hölder continuous up to the boundary with some α>0. AU - Gerencser, Mate ID - 6232 IS - 2 JF - Annals of Probability SN - 00911798 TI - Boundary regularity of stochastic PDEs VL - 47 ER - TY - JOUR AB - Gravitropism is an adaptive response that orients plant growth parallel to the gravity vector. Asymmetric distribution of the phytohormone auxin is a necessary prerequisite to the tropic bending both in roots and shoots. During hypocotyl gravitropic response, the PIN3 auxin transporter polarizes within gravity-sensing cells to redirect intercellular auxin fluxes. First gravity-induced PIN3 polarization to the bottom cell mem- branes leads to the auxin accumulation at the lower side of the organ, initiating bending and, later, auxin feedback-mediated repolarization restores symmetric auxin distribution to terminate bending. Here, we per- formed a forward genetic screen to identify regulators of both PIN3 polarization events during gravitropic response. We searched for mutants with defective PIN3 polarizations based on easy-to-score morphological outputs of decreased or increased gravity-induced hypocotyl bending. We identified the number of hypocotyl reduced bending (hrb) and hypocotyl hyperbending (hhb) mutants, revealing that reduced bending corre- lated typically with defective gravity-induced PIN3 relocation whereas all analyzed hhb mutants showed defects in the second, auxin-mediated PIN3 relocation. Next-generation sequencing-aided mutation map- ping identified several candidate genes, including SCARECROW and ACTIN2, revealing roles of endodermis specification and actin cytoskeleton in the respective gravity- and auxin-induced PIN polarization events. The hypocotyl gravitropism screen thus promises to provide novel insights into mechanisms underlying cell polarity and plant adaptive development. AU - Rakusová, Hana AU - Han, Huibin AU - Valošek, Petr AU - Friml, Jiří ID - 6262 IS - 6 JF - The Plant Journal SN - 0960-7412 TI - Genetic screen for factors mediating PIN polarization in gravistimulated Arabidopsis thaliana hypocotyls VL - 98 ER -