@article{14795, abstract = {Metazoan development relies on the formation and remodeling of cell-cell contacts. Dynamic reorganization of adhesion receptors and the actomyosin cell cortex in space and time plays a central role in cell-cell contact formation and maturation. Nevertheless, how this process is mechanistically achieved when new contacts are formed remains unclear. Here, by building a biomimetic assay composed of progenitor cells adhering to supported lipid bilayers functionalized with E-cadherin ectodomains, we show that cortical F-actin flows, driven by the depletion of myosin-2 at the cell contact center, mediate the dynamic reorganization of adhesion receptors and cell cortex at the contact. E-cadherin-dependent downregulation of the small GTPase RhoA at the forming contact leads to both a depletion of myosin-2 and a decrease of F-actin at the contact center. At the contact rim, in contrast, myosin-2 becomes enriched by the retraction of bleb-like protrusions, resulting in a cortical tension gradient from the contact rim to its center. This tension gradient, in turn, triggers centrifugal F-actin flows, leading to further accumulation of F-actin at the contact rim and the progressive redistribution of E-cadherin from the contact center to the rim. Eventually, this combination of actomyosin downregulation and flows at the contact determines the characteristic molecular organization, with E-cadherin and F-actin accumulating at the contact rim, where they are needed to mechanically link the contractile cortices of the adhering cells.}, author = {Arslan, Feyza N and Hannezo, Edouard B and Merrin, Jack and Loose, Martin and Heisenberg, Carl-Philipp J}, issn = {1879-0445}, journal = {Current Biology}, number = {1}, pages = {171--182.e8}, publisher = {Elsevier}, title = {{Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts}}, doi = {10.1016/j.cub.2023.11.067}, volume = {34}, year = {2024}, } @article{14479, abstract = {In animals, parasitic infections impose significant fitness costs.1,2,3,4,5,6 Infected animals can alter their feeding behavior to resist infection,7,8,9,10,11,12 but parasites can manipulate animal foraging behavior to their own benefits.13,14,15,16 How nutrition influences host-parasite interactions is not well understood, as studies have mainly focused on the host and less on the parasite.9,12,17,18,19,20,21,22,23 We used the nutritional geometry framework24 to investigate the role of amino acids (AA) and carbohydrates (C) in a host-parasite system: the Argentine ant, Linepithema humile, and the entomopathogenic fungus, Metarhizium brunneum. First, using 18 diets varying in AA:C composition, we established that the fungus performed best on the high-amino-acid diet 1:4. Second, we found that the fungus reached this optimal diet when given various diet pairings, revealing its ability to cope with nutritional challenges. Third, we showed that the optimal fungal diet reduced the lifespan of healthy ants when compared with a high-carbohydrate diet but had no effect on infected ants. Fourth, we revealed that infected ant colonies, given a choice between the optimal fungal diet and a high-carbohydrate diet, chose the optimal fungal diet, whereas healthy colonies avoided it. Lastly, by disentangling fungal infection from host immune response, we demonstrated that infected ants foraged on the optimal fungal diet in response to immune activation and not as a result of parasite manipulation. Therefore, we revealed that infected ant colonies chose a diet that is costly for survival in the long term but beneficial in the short term—a form of collective self-medication.}, author = {Csata, Eniko and Perez-Escudero, Alfonso and Laury, Emmanuel and Leitner, Hanna and Latil, Gerard and Heinze, Juerge and Simpson, Stephen and Cremer, Sylvia and Dussutour, Audrey}, issn = {1879-0445}, journal = {Current Biology}, number = {4}, pages = {902--909.e6}, publisher = {Elsevier}, title = {{Fungal infection alters collective nutritional intake of ant colonies}}, doi = {10.1016/j.cub.2024.01.017}, volume = {34}, year = {2024}, } @article{11351, abstract = {One hallmark of plant cells is their cell wall. They protect cells against the environment and high turgor and mediate morphogenesis through the dynamics of their mechanical and chemical properties. The walls are a complex polysaccharidic structure. Although their biochemical composition is well known, how the different components organize in the volume of the cell wall and interact with each other is not well understood and yet is key to the wall’s mechanical properties. To investigate the ultrastructure of the plant cell wall, we imaged the walls of onion (Allium cepa) bulbs in a near-native state via cryo-focused ion beam milling (cryo-FIB milling) and cryo-electron tomography (cryo-ET). This allowed the high-resolution visualization of cellulose fibers in situ. We reveal the coexistence of dense fiber fields bathed in a reticulated matrix we termed “meshing,” which is more abundant at the inner surface of the cell wall. The fibers adopted a regular bimodal angular distribution at all depths in the cell wall and bundled according to their orientation, creating layers within the cell wall. Concomitantly, employing homogalacturonan (HG)-specific enzymatic digestion, we observed changes in the meshing, suggesting that it is—at least in part—composed of HG pectins. We propose the following model for the construction of the abaxial epidermal primary cell wall: the cell deposits successive layers of cellulose fibers at −45° and +45° relative to the cell’s long axis and secretes the surrounding HG-rich meshing proximal to the plasma membrane, which then migrates to more distal regions of the cell wall.}, author = {Nicolas, William J. and Fäßler, Florian and Dutka, Przemysław and Schur, Florian KM and Jensen, Grant and Meyerowitz, Elliot}, issn = {0960-9822}, journal = {Current Biology}, keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology}, number = {11}, pages = {P2375--2389}, publisher = {Elsevier}, title = {{Cryo-electron tomography of the onion cell wall shows bimodally oriented cellulose fibers and reticulated homogalacturonan networks}}, doi = {10.1016/j.cub.2022.04.024}, volume = {32}, year = {2022}, } @article{10834, abstract = {Hematopoietic-specific protein 1 (Hem1) is an essential subunit of the WAVE regulatory complex (WRC) in immune cells. WRC is crucial for Arp2/3 complex activation and the protrusion of branched actin filament networks. Moreover, Hem1 loss of function in immune cells causes autoimmune diseases in humans. Here, we show that genetic removal of Hem1 in macrophages diminishes frequency and efficacy of phagocytosis as well as phagocytic cup formation in addition to defects in lamellipodial protrusion and migration. Moreover, Hem1-null macrophages displayed strong defects in cell adhesion despite unaltered podosome formation and concomitant extracellular matrix degradation. Specifically, dynamics of both adhesion and de-adhesion as well as concomitant phosphorylation of paxillin and focal adhesion kinase (FAK) were significantly compromised. Accordingly, disruption of WRC function in non-hematopoietic cells coincided with both defects in adhesion turnover and altered FAK and paxillin phosphorylation. Consistently, platelets exhibited reduced adhesion and diminished integrin αIIbβ3 activation upon WRC removal. Interestingly, adhesion phenotypes, but not lamellipodia formation, were partially rescued by small molecule activation of FAK. A full rescue of the phenotype, including lamellipodia formation, required not only the presence of WRCs but also their binding to and activation by Rac. Collectively, our results uncover that WRC impacts on integrin-dependent processes in a FAK-dependent manner, controlling formation and dismantling of adhesions, relevant for properly grabbing onto extracellular surfaces and particles during cell edge expansion, like in migration or phagocytosis.}, author = {Stahnke, Stephanie and Döring, Hermann and Kusch, Charly and de Gorter, David J.J. and Dütting, Sebastian and Guledani, Aleks and Pleines, Irina and Schnoor, Michael and Sixt, Michael K and Geffers, Robert and Rohde, Manfred and Müsken, Mathias and Kage, Frieda and Steffen, Anika and Faix, Jan and Nieswandt, Bernhard and Rottner, Klemens and Stradal, Theresia E.B.}, issn = {0960-9822}, journal = {Current Biology}, keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology}, number = {10}, pages = {2051--2064.e8}, publisher = {Elsevier}, title = {{Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion}}, doi = {10.1016/j.cub.2021.02.043}, volume = {31}, year = {2021}, } @article{8824, abstract = {Plants are able to orient their growth according to gravity, which ultimately controls both shoot and root architecture.1 Gravitropism is a dynamic process whereby gravistimulation induces the asymmetric distribution of the plant hormone auxin, leading to asymmetric growth, organ bending, and subsequent reset of auxin distribution back to the original pre-gravistimulation situation.1, 2, 3 Differential auxin accumulation during the gravitropic response depends on the activity of polarly localized PIN-FORMED (PIN) auxin-efflux carriers.1, 2, 3, 4 In particular, the timing of this dynamic response is regulated by PIN2,5,6 but the underlying molecular mechanisms are poorly understood. Here, we show that MEMBRANE ASSOCIATED KINASE REGULATOR2 (MAKR2) controls the pace of the root gravitropic response. We found that MAKR2 is required for the PIN2 asymmetry during gravitropism by acting as a negative regulator of the cell-surface signaling mediated by the receptor-like kinase TRANSMEMBRANE KINASE1 (TMK1).2,7, 8, 9, 10 Furthermore, we show that the MAKR2 inhibitory effect on TMK1 signaling is antagonized by auxin itself, which triggers rapid MAKR2 membrane dissociation in a TMK1-dependent manner. Our findings suggest that the timing of the root gravitropic response is orchestrated by the reversible inhibition of the TMK1 signaling pathway at the cell surface.}, author = {Marquès-Bueno, MM and Armengot, L and Noack, LC and Bareille, J and Rodriguez Solovey, Lesia and Platre, MP and Bayle, V and Liu, M and Opdenacker, D and Vanneste, S and Möller, BK and Nimchuk, ZL and Beeckman, T and Caño-Delgado, AI and Friml, Jiří and Jaillais, Y}, issn = {1879-0445}, journal = {Current Biology}, number = {1}, publisher = {Elsevier}, title = {{Auxin-regulated reversible inhibition of TMK1 signaling by MAKR2 modulates the dynamics of root gravitropism}}, doi = {10.1016/j.cub.2020.10.011}, volume = {31}, year = {2021}, } @article{9290, abstract = {Polar subcellular localization of the PIN exporters of the phytohormone auxin is a key determinant of directional, intercellular auxin transport and thus a central topic of both plant cell and developmental biology. Arabidopsis mutants lacking PID, a kinase that phosphorylates PINs, or the MAB4/MEL proteins of unknown molecular function display PIN polarity defects and phenocopy pin mutants, but mechanistic insights into how these factors convey PIN polarity are missing. Here, by combining protein biochemistry with quantitative live-cell imaging, we demonstrate that PINs, MAB4/MELs, and AGC kinases interact in the same complex at the plasma membrane. MAB4/MELs are recruited to the plasma membrane by the PINs and in concert with the AGC kinases maintain PIN polarity through limiting lateral diffusion-based escape of PINs from the polar domain. The PIN-MAB4/MEL-PID protein complex has self-reinforcing properties thanks to positive feedback between AGC kinase-mediated PIN phosphorylation and MAB4/MEL recruitment. We thus uncover the molecular mechanism by which AGC kinases and MAB4/MEL proteins regulate PIN localization and plant development.}, author = {Glanc, Matous and Van Gelderen, K and Hörmayer, Lukas and Tan, Shutang and Naramoto, S and Zhang, Xixi and Domjan, David and Vcelarova, L and Hauschild, Robert and Johnson, Alexander J and de Koning, E and van Dop, M and Rademacher, E and Janson, S and Wei, X and Molnar, Gergely and Fendrych, Matyas and De Rybel, B and Offringa, R and Friml, Jiří}, issn = {1879-0445}, journal = {Current Biology}, number = {9}, pages = {1918--1930}, publisher = {Elsevier}, title = {{AGC kinases and MAB4/MEL proteins maintain PIN polarity by limiting lateral diffusion in plant cells}}, doi = {10.1016/j.cub.2021.02.028}, volume = {31}, year = {2021}, } @article{6979, author = {Kopf, Aglaja and Sixt, Michael K}, issn = {1879-0445}, journal = {Current Biology}, number = {20}, pages = {R1091--R1093}, publisher = {Cell Press}, title = {{Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal}}, doi = {10.1016/j.cub.2019.08.068}, volume = {29}, year = {2019}, } @article{12190, abstract = {Meiotic crossover frequency varies within genomes, which influences genetic diversity and adaptation. In turn, genetic variation within populations can act to modify crossover frequency in cis and trans. To identify genetic variation that controls meiotic crossover frequency, we screened Arabidopsis accessions using fluorescent recombination reporters. We mapped a genetic modifier of crossover frequency in Col × Bur populations of Arabidopsis to a premature stop codon within TBP-ASSOCIATED FACTOR 4b (TAF4b), which encodes a subunit of the RNA polymerase II general transcription factor TFIID. The Arabidopsis taf4b mutation is a rare variant found in the British Isles, originating in South-West Ireland. Using genetics, genomics, and immunocytology, we demonstrate a genome-wide decrease in taf4b crossovers, with strongest reduction in the sub-telomeric regions. Using RNA sequencing (RNA-seq) from purified meiocytes, we show that TAF4b expression is meiocyte enriched, whereas its paralog TAF4 is broadly expressed. Consistent with the role of TFIID in promoting gene expression, RNA-seq of wild-type and taf4b meiocytes identified widespread transcriptional changes, including in genes that regulate the meiotic cell cycle and recombination. Therefore, TAF4b duplication is associated with acquisition of meiocyte-specific expression and promotion of germline transcription, which act directly or indirectly to elevate crossovers. This identifies a novel mode of meiotic recombination control via a general transcription factor.}, author = {Lawrence, Emma J. and Gao, Hongbo and Tock, Andrew J. and Lambing, Christophe and Blackwell, Alexander R. and Feng, Xiaoqi and Henderson, Ian R.}, issn = {0960-9822}, journal = {Current Biology}, keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology}, number = {16}, pages = {2676--2686.e3}, publisher = {Elsevier BV}, title = {{Natural variation in TBP-ASSOCIATED FACTOR 4b controls meiotic crossover and germline transcription in Arabidopsis}}, doi = {10.1016/j.cub.2019.06.084}, volume = {29}, year = {2019}, } @article{11074, author = {Hatch, Emily M. and HETZER, Martin W}, issn = {0960-9822}, journal = {Current Biology}, keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology}, number = {10}, pages = {PR397--R399}, publisher = {Elsevier}, title = {{Chromothripsis}}, doi = {10.1016/j.cub.2015.02.033}, volume = {25}, year = {2015}, } @article{9489, abstract = {Cytosine methylation is an ancient process with conserved enzymology but diverse biological functions that include defense against transposable elements and regulation of gene expression. Here we will discuss the evolution and biological significance of eukaryotic DNA methylation, the likely drivers of that evolution, and major remaining mysteries.}, author = {Zemach, Assaf and Zilberman, Daniel}, issn = {1879-0445}, journal = {Current Biology}, number = {17}, pages = {R780--R785}, publisher = {Elsevier}, title = {{Evolution of eukaryotic DNA methylation and the pursuit of safer sex}}, doi = {10.1016/j.cub.2010.07.007}, volume = {20}, year = {2010}, } @article{7752, author = {Robinson, Matthew Richard and Pilkington, Jill G. and Clutton-Brock, Tim H. and Pemberton, Josephine M. and Kruuk, Loeske. E.B.}, issn = {0960-9822}, journal = {Current Biology}, number = {10}, pages = {751--757}, publisher = {Elsevier}, title = {{Environmental heterogeneity generates fluctuating selection on a secondary sexual trait}}, doi = {10.1016/j.cub.2008.04.059}, volume = {18}, year = {2008}, } @article{6149, author = {Olofsson, Birgitta and de Bono, Mario}, issn = {0960-9822}, journal = {Current Biology}, number = {5}, pages = {R204--R206}, publisher = {Elsevier}, title = {{Sleep: dozy worms and sleepy flies}}, doi = {10.1016/j.cub.2008.01.002}, volume = {18}, year = {2008}, } @article{6150, author = {Gumienny, Tina L. and MacNeil, Lesley T. and Wang, Huang and de Bono, Mario and Wrana, Jeffrey L. and Padgett, Richard W.}, issn = {0960-9822}, journal = {Current Biology}, number = {2}, pages = {159--164}, publisher = {Elsevier}, title = {{Glypican LON-2 is a conserved negative regulator of BMP-like signaling in Caenorhabditis elegans}}, doi = {10.1016/j.cub.2006.11.065}, volume = {17}, year = {2007}, } @article{6152, author = {Rogers, Candida and Persson, Annelie and Cheung, Benny and de Bono, Mario}, issn = {0960-9822}, journal = {Current Biology}, number = {7}, pages = {649--659}, publisher = {Elsevier}, title = {{Behavioral motifs and neural pathways coordinating O2 responses and aggregation in C. elegans}}, doi = {10.1016/j.cub.2006.03.023}, volume = {16}, year = {2006}, } @article{6154, author = {Cheung, Benny H.H. and Cohen, Merav and Rogers, Candida and Albayram, Onder and de Bono, Mario}, issn = {0960-9822}, journal = {Current Biology}, number = {10}, pages = {905--917}, publisher = {Elsevier}, title = {{Experience-dependent modulation of C. elegans behavior by ambient oxygen}}, doi = {10.1016/j.cub.2005.04.017}, volume = {15}, year = {2005}, } @article{9491, abstract = {Cytosine DNA methylation in vertebrates is widespread, but methylation in plants is found almost exclusively at transposable elements and repetitive DNA [1]. Within regions of methylation, methylcytosines are typically found in CG, CNG, and asymmetric contexts. CG sites are maintained by a plant homolog of mammalian Dnmt1 acting on hemi-methylated DNA after replication. Methylation of CNG and asymmetric sites appears to be maintained at each cell cycle by other mechanisms. We report a new type of DNA methylation in Arabidopsis, dense CG methylation clusters found at scattered sites throughout the genome. These clusters lack non-CG methylation and are preferentially found in genes, although they are relatively deficient toward the 5′ end. CG methylation clusters are present in lines derived from different accessions and in mutants that eliminate de novo methylation, indicating that CG methylation clusters are stably maintained at specific sites. Because 5-methylcytosine is mutagenic, the appearance of CG methylation clusters over evolutionary time predicts a genome-wide deficiency of CG dinucleotides and an excess of C(A/T)G trinucleotides within transcribed regions. This is exactly what we find, implying that CG methylation clusters have contributed profoundly to plant gene evolution. We suggest that CG methylation clusters silence cryptic promoters that arise sporadically within transcription units.}, author = {Tran, Robert K. and Henikoff, Jorja G. and Zilberman, Daniel and Ditt, Renata F. and Jacobsen, Steven E. and Henikoff, Steven}, issn = {1879-0445}, journal = {Current Biology}, number = {2}, pages = {154--159}, publisher = {Elsevier}, title = {{DNA methylation profiling identifies CG methylation clusters in Arabidopsis genes}}, doi = {10.1016/j.cub.2005.01.008}, volume = {15}, year = {2005}, } @article{6155, abstract = {The genome of the nematode Caenorhabditis elegans encodes seven soluble guanylate cyclases (sGCs) [1]. In mammals, sGCs function as α/β heterodimers activated by gaseous ligands binding to a haem prosthetic group 2, 3. The principal activator is nitric oxide, which acts through sGCs to regulate diverse cellular events. In C. elegans the function of sGCs is mysterious: the worm genome does not appear to encode nitric oxide synthase, and all C. elegans sGC subunits are more closely related to mammalian β than α subunits [1]. Here, we show that two of the seven C. elegans sGCs, GCY-35 and GCY-36, promote aggregation behavior. gcy-35 and gcy-36 are expressed in a small number of neurons. These include the body cavity neurons AQR, PQR, and URX, which are directly exposed to the blood equivalent of C. elegans and regulate aggregation behavior [4]. We show that GCY-35 and GCY-36 act as α-like and β-like sGC subunits and that their function in the URX sensory neurons is sufficient for strong nematode aggregation. Neither GCY-35 nor GCY-36 is absolutely required for C. elegans to aggregate. Instead, these molecules may transduce one of several pathways that induce C. elegans to aggregate or may modulate aggregation by responding to cues in C. elegans body fluid.}, author = {Cheung, Benny H.H and Arellano-Carbajal, Fausto and Rybicki, Irene and de Bono, Mario}, issn = {0960-9822}, journal = {Current Biology}, number = {12}, pages = {1105--1111}, publisher = {Elsevier}, title = {{Soluble guanylate cyclases act in neurons exposed to the body fluid to promote C. elegans aggregation behavior}}, doi = {10.1016/j.cub.2004.06.027}, volume = {14}, year = {2004}, } @article{9493, abstract = {In a number of organisms, transgenes containing transcribed inverted repeats (IRs) that produce hairpin RNA can trigger RNA-mediated silencing, which is associated with 21-24 nucleotide small interfering RNAs (siRNAs). In plants, IR-driven RNA silencing also causes extensive cytosine methylation of homologous DNA in both the transgene "trigger" and any other homologous DNA sequences--"targets". Endogenous genomic sequences, including transposable elements and repeated elements, are also subject to RNA-mediated silencing. The RNA silencing gene ARGONAUTE4 (AGO4) is required for maintenance of DNA methylation at several endogenous loci and for the establishment of methylation at the FWA gene. Here, we show that mutation of AGO4 substantially reduces the maintenance of DNA methylation triggered by IR transgenes, but AGO4 loss-of-function does not block the initiation of DNA methylation by IRs. AGO4 primarily affects non-CG methylation of the target sequences, while the IR trigger sequences lose methylation in all sequence contexts. Finally, we find that AGO4 and the DRM methyltransferase genes are required for maintenance of siRNAs at a subset of endogenous sequences, but AGO4 is not required for the accumulation of IR-induced siRNAs or a number of endogenous siRNAs, suggesting that AGO4 may function downstream of siRNA production.}, author = {Zilberman, Daniel and Cao, Xiaofeng and Johansen, Lisa K. and Xie, Zhixin and Carrington, James C. and Jacobsen, Steven E.}, issn = {1879-0445}, journal = {Current Biology}, number = {13}, pages = {1214--1220}, publisher = {Elsevier}, title = {{Role of Arabidopsis ARGONAUTE4 in RNA-directed DNA methylation triggered by inverted repeats}}, doi = {10.1016/j.cub.2004.06.055}, volume = {14}, year = {2004}, } @article{9495, abstract = {RNA interference is a conserved process in which double-stranded RNA is processed into 21–25 nucleotide siRNAs that trigger posttranscriptional gene silencing. In addition, plants display a phenomenon termed RNA-directed DNA methylation (RdDM) in which DNA with sequence identity to silenced RNA is de novo methylated at its cytosine residues. This methylation is not only at canonical CpG sites but also at cytosines in CpNpG and asymmetric sequence contexts. In this report, we study the role of the DRM and CMT3 DNA methyltransferase genes in the initiation and maintenance of RdDM. Neither drm nor cmt3 mutants affected the maintenance of preestablished RNA-directed CpG methylation. However, drm mutants showed a nearly complete loss of asymmetric methylation and a partial loss of CpNpG methylation. The remaining asymmetric and CpNpG methylation was dependent on the activity of CMT3, showing that DRM and CMT3 act redundantly to maintain non-CpG methylation. These DNA methyltransferases appear to act downstream of siRNAs, since drm1 drm2 cmt3 triple mutants show a lack of non-CpG methylation but elevated levels of siRNAs. Finally, we demonstrate that DRM activity is required for the initial establishment of RdDM in all sequence contexts including CpG, CpNpG, and asymmetric sites.}, author = {Cao, Xiaofeng and Aufsatz, Werner and Zilberman, Daniel and Mette, M.Florian and Huang, Michael S. and Matzke, Marjori and Jacobsen, Steven E.}, issn = {1879-0445}, journal = {Current Biology}, number = {24}, pages = {2212--2217}, publisher = {Elsevier}, title = {{Role of the DRM and CMT3 methyltransferases in RNA-directed DNA methylation}}, doi = {10.1016/j.cub.2003.11.052}, volume = {13}, year = {2003}, } @article{4169, abstract = {Background: During vertebrate gastrulation, cell polarization and migration are core components in the cellular rearrangements that lead to the formation of the three germ layers, ectoderm, mesoderm, and endoderm. Previous studies have implicated the Wnt/planar cell polarity (PCP) signaling pathway in controlling cell morphology and movement during gastrulation. However, cell polarization and directed cell migration are reduced but not completely abolished in the absence of Wnt/PCP signals; this observation indicates that other signaling pathways must be involved. Results: We show that Phosphoinositide 3-Kinases (PI3Ks) are required at the onset of zebrafish gastrulation in mesendodermal cells for process formation and cell polarization. Platelet Derived Growth Factor (PDGF) functions upstream of PI3K, while Protein Kinase B (PKB), a downstream effector of PI3K activity, localizes to the leading edge of migrating mesendodermal cells. In the absence of PI3K activity, PKB localization and cell polarization are strongly reduced in mesendodermal cells and are followed by slower but still highly coordinated and directed movements of these cells. Conclusions: We have identified a novel role of a signaling pathway comprised of PDGF, PI3K, and PKB in the control of morphogenetic cell movements during gastrulation. Furthermore, our findings provide insight into the relationship between cell polarization and directed cell migration at the onset of zebrafish gastrulation.}, author = {Montero, Juan and Kilian, Beate and Chan, Joanne and Bayliss, Peter and Heisenberg, Carl-Philipp J}, issn = {1879-0445}, journal = {Current Biology}, number = {15}, pages = {1279 -- 1289}, publisher = {Cell Press}, title = {{Phosphoinositide 3-kinase is required for process outgrowth and cell polarization of gastrulating mesendodermal cells}}, doi = {10.1016/S0960-9822(03)00505-0}, volume = {13}, year = {2003}, }