Microtubules Enable the Planar Cell Polarity of Airway Cilia

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Highlights? PCP proteins are asymmetric at apical junctions in the airways before ciliogenesis ? PCP protein asymmetry and cilium orientation emerge gradually during development ? Cilium misorientation correlates with loss of PCP protein asymmetry in PCP mutants ? Microtubules appear to organize cilium orientation and PCP protein asymmetry     

Calponin 2 Acts As an Effector of Noncanonical Wnt-Mediated Cell Polarization during Neural Crest Cell Migration

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Highlights? Cnn2 is expressed in NCCs and required for their migration in frogs and chicks ? Cnn2 is inactivated by noncanonical Wnt signaling ? Loss of Cnn2 causes a switch from cortical actin to central stress fibers ? Cnn2 polarizes the actin cytoskeleton downstream of PCP     

An ERK-p38 Subnetwork Coordinates Host Cell Apoptosis and Necrosis during Coxsackievirus B3 Infection

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Highlights? Intracellular signaling predicts the fate of coxsackievirus B3 (CVB3)-infected cells ? p38 and ERK signaling pathways are tightly interconnected during CVB3 infection ? CVB3-induced apoptosis of cardiomyocytes is inhibited by ERK5 and ERK1/2 pathways ? CVB3 induces necrosis of cardiomyocytes via p38 activation     

Spatial Restriction of FGF Signaling by a Matrix Metalloprotease Controls Branching Morphogenesis

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Highlights? Drosophila Matrix Metalloprotease (Mmp) inhibits FGF signaling ? An FGF – MMP feedback loop regulates branching morphogenesis ? Mmp2 spatially regulates FGF signaling in epithelia     

Peripheral Nerve-Derived CXCL12 and VEGF-A Regulate the Patterning of Arterial Vessel Branching in Developing Limb Skin

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Highlights? Cxcr4 is expressed by a subset of endothelial cells in the capillary network ? Genetic inactivation of Cxcl12-Cxcr4 signaling perturbs nerve-vessel alignment ? Cxcl12 controls endothelial migration, whereas VEGF directs arterial differentiation     

Supernumerary centrosomes nucleate extra cilia and compromise primary cilium signaling

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Highlights? Supernumerary centrosomes nucleate cilia, resulting in superciliated cells (SCC) ? Ciliary proteins are reduced in concentration in SCC, compromising signaling ? Presence of extra cilia disrupts epithelial organization in 3D spheroid culture ? Extra cilia may contribute to disease phenotypes by disrupting signaling     

FAM3B PANDER and FAM3C ILEI Represent a Distinct Class of Signaling Molecules with a Non-Cytokine-like Fold

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Highlights? Contrary to previous predictions FAM3B PANDER exhibits a new non-cytokine-like fold ? The new fold is also conserved in FAM3C ILEI and involved in cancer and tumor formation ? FAM3 is a new class of signaling molecules different from currently known cytokines     

Quiescent and Active Hippocampal Neural Stem Cells with Distinct Morphologies Respond Selectively to Physiological and Pathological Stimuli and Aging

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Highlights? Notch signaling defines morphologically distinct hippocampal stem cell populations ? Radial and horizontal hippocampal stem cells depend on canonical Notch signaling ? Different neural stem cell subpopulations respond selectively to neurogenic stimuli ? Aging results in a reversible transition of stem cells to a quiescent state     

The Ciliary G-Protein-Coupled Receptor Gpr161 Negatively Regulates the Sonic Hedgehog Pathway via cAMP Signaling

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Highlights? The GPCR Gpr161 localizes to primary cilia in a Tulp3/IFT-A-dependent manner ? Complete loss of Gpr161 increases Shh signaling in the mouse neural tube ? Gpr161 couples protein kinase A activation to Shh signaling via cAMP signaling ? Shh signaling internalizes Gpr161 from the cilia, preventing its activity     

Cofactors required for TLR7- and TLR9-dependent innate immune responses

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Highlights? RNAi and systems-based analysis identified 190 TLR7/9 signaling cofactors ? Pathway crossprofiling enabled mapping cofactors to specific NFκB signaling modules ? HRS is a mediator of ubiquitin-dependent nondegradative endosomal TLR sorting     

Organism-Scale Modeling of Early Drosophila Patterning via Bone Morphogenetic Proteins

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Highlights? Capturing 3D spatiotemporal content of expression data increases model utility ? Embryo geometry shapes signaling; prepatterns compensate in misshapen embryos ? Cell-surface binding proteins compensate for weak ligand/inhibitor/receptor binding ? BMP-mediated patterning is “nearly” scale-invariant     

Intestinal Tumorigenesis Initiated by Dedifferentiation and Acquisition of Stem-Cell-like Properties

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Highlights? Epithelial nonstem cells can be reprogrammed into tumor-initiating cells ? Dedifferentiation depends on degree of Wnt signaling ? Wnt signaling is enhanced by NFkB via the coactivator CBP ? Differentiation of stem cells into nonstem cells is bidirectional     

Dopamine controls neurogenesis in the adult salamander midbrain in homeostasis and during regeneration of dopamine neurons

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Highlights? Regeneration of midbrain dopamine neurons depends on decreased dopamine signaling ? L-dopa inhibits ependymoglia cell proliferation during dopamine neuron regeneration ? Proliferation of ependymoglia cells is constantly suppressed by dopamine signaling ? Inhibition of dopamine signaling evokes neurogenesis by quiescent ependymoglia cells     

Conserved and Divergent Roles of FGF Signaling in Mouse Epiblast Stem Cells and Human Embryonic Stem Cells

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Highlights? Nanog is a direct target of Activin and SMAD2/3 but not FGF-ERK in EpiSCs ? FGF signaling inhibits neuroectodermal commitment of EpiSCs and hESCs ? FGF inhibition relieves Klf2 repression and reverts EpiSCs to an ESC-like state ? mESCs transition to an EpiSC-like state with LIF inhibition and FGF activation     

Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

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Highlights? Perivascular niche nitric oxide activates Notch in PDGF-induced gliomas ? Notch signaling drives tumor stem-like characteristics and reduces survival ? Loss of eNOS activity decreases tumor stem-like characteristics ? Suppressing eNOS activity prolongs survival in glioma-bearing mice     

Bax Exists in a Dynamic Equilibrium between the Cytosol and Mitochondria to Control Apoptotic Priming

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Highlights? Bax exists in equilibrium between the cytosol and mitochondria ? The retrotranslocation of Bax is independent of direct-activator BH3 proteins ? Changes in survival signaling modulate the dissociation rate of mitochondrial Bax ? Accumulation of Bax on mitochondria sensitizes cells to apoptosis     

ANGUSTIFOLIA3 Signaling Coordinates Proliferation between Clonally Distinct Cells in Leaves

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Highlights? AN3 is produced specifically in mesophyll cells and moves into epidermal cells ? AN3 participates in the control of epidermal cell proliferation ? AN3 signaling is essential for normal leaf development ? AN3 movement does not require the action of the type II chaperonin complex     

Hypothalamic mTORC1 Signaling Controls Sympathetic Nerve Activity and Arterial Pressure and Mediates Leptin Effects

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Highlights? Activation of hypothalamic mTORC1 increases sympathetic traffic and arterial pressure ? The sympathetic and hemodynamic effects of leptin require hypothalamic mTORC1 ? PI3K links the leptin receptor to mTORC1 signaling in the hypothalamus ? Modulating PI3K activity perturbs the sympathetic and hemodynamic functions     

Structural Mechanism of CCM3 Heterodimerization with GCKIII Kinases

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Highlights? Crystal structure of CCM3-MST4 heterodimeric complex ? Structural mechanism driving CCM3-GCKIII heterodimerization ? Conformational changes required for CCM3-GCKIII heterodimerization ? Synergistic effects of CCM3-MST4 complex on cell proliferation and migration     

Robustness and Epistasis in the C. elegans Vulval Signaling Network Revealed by Pathway Dosage Modulation

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Highlights? A phase map of cell fate patterns is built as a function of signaling pathway dose ? The vulva system can buffer a 4-fold variation in mean lin-3/egf mRNA number ? The major role of LIN-12/Notch in the vulva is to promote the 2° fate ? Inhibition of 1° fate by LIN-12 is important when lin-3 dose is mildly increased