Directional guidance of cells via gradients chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous chemokine CCL21 within mouse skin show that they guide dendritic toward lymphatic vessels. Quantitative imaging reveals depots endothelial steeply decaying perilymphatic interstitium. These match migratory patterns cells, which...

In the developing fly wing, secreted morphogens such as Decapentaplegic (Dpp) and Wingless (Wg) form gradients of concentration providing positional information. Dpp forms a longer-range gradient than Wg. To understand how range is controlled, we measured four key kinetic parameters governing morphogen spreading: production rate, effective diffusion coefficient, degradation immobile fraction. The had different values for versus addition, Dynamin-dependent endocytosis was required spreading...

Significance In many infections, multiple microbial species are present simultaneously. Such polymicrobial infections can be viewed as small ecosystems. Do bacteria in these communities interact with each other? If so, do interactions affect the stability of ecosystem, particular, when antibiotics present? We focus on urinary tract and demonstrate that there ample ecological between different bacterial species, both presence absence antibiotics. further show they crucially ecosystem...

Like many developing tissues, the vertebrate neural tube is patterned by antiparallel morphogen gradients. To understand how these inputs are interpreted, we measured signaling and target gene expression in mouse embryos chick ex vivo assays. From data, derived validated a characteristic decoding map that relates input to positional identity of progenitors. Analysis observed responses indicates underlying interpretation strategy minimizes patterning errors response joint noisy opposing We...

Development requires tissue growth as well cell diversification. To address how these processes are coordinated, we analyzed the development of molecularly distinct domains neural progenitors in mouse and chick tube. We show that during development, undergo changes size do not scale with overall size. Our data domain proportions first established by opposing morphogen gradients subsequently controlled domain-specific regulation differentiation rate but differences proliferation rate....

Morphogen concentration gradients provide positional information by activating target genes in a concentration-dependent manner. Recent reports show that the gradient of syncytial morphogen Bicoid seems to precise determine gene domains. For secreted morphogenetic ligands, precision gradients, signal transduction and reliability expression domains have not been studied. Here we investigate these issues for TGF-beta-type Dpp. We first studied theoretically how cell-to-cell variability source,...

Both Gram-positive and Gram-negative bacteria contain bactoprenol-dependent biosynthetic pathways expressing non-essential cell surface polysaccharides that function as virulence factors. Although these polymers are not required for bacterial viability in vitro, genes many of the conditionally essential: they cannot be deleted except strains incapable initiating polymer synthesis. We report a cell-based, pathway-specific strategy to screen small molecule inhibitors essential enzymes. The...

The emergence of drug resistant pathogens is a serious public health problem. It long-standing goal to predict rates resistance evolution and design optimal treatment strategies accordingly. To this end, it crucial reveal the underlying causes drug-specific differences in evolutionary dynamics leading resistance. However, remains largely unknown why via spontaneous mutations diversity mutational paths vary substantially between drugs. Here we comprehensively quantify distribution fitness...

Antibiotics elicit drastic changes in microbial gene expression, including the induction of stress response genes. While certain responses are known to "cross-protect" bacteria from other stressors, it is unclear whether cellular antibiotics have a similar protective role. By measuring genome-wide transcriptional dynamics Escherichia coli four antibiotics, we found that trimethoprim induces rapid acid protects subsequent exposure acid. Combining microfluidics with time-lapse imaging monitor...

Cellular locomotion is a central hallmark of eukaryotic life. It governed by cell-extrinsic molecular factors, which can either emerge in the soluble phase or as immobilized, often adhesive ligands. To encode for direction, every cue must be present spatial temporal gradient. Here, we developed microfluidic chamber that allows measurement cell migration combined response to surface immobilized and gradients. As proof principle study dendritic cells their major guidance cues, chemokines. The...

Genetic perturbations that affect bacterial resistance to antibiotics have been characterized genome-wide, but how do such interact with subsequent evolutionary adaptation the drug? Here, we show strong epistasis between mutations and systematically identified genes can be exploited control spontaneous evolution. We evolved hundreds of Escherichia coli K-12 mutant populations in parallel, using a robotic platform tightly controls population size selection pressure. find global...

Developing cells acquire positional information by reading the graded distribution of morphogens. In Drosophila, Dpp morphogen forms a long-range concentration gradient spreading from restricted source in developing wing. It has been assumed that spreads extracellular diffusion. Under this assumption, main role endocytosis formation is to downregulate receptors at cell surface. These surface bind ligand and thereby interfere with its movement. Recent experiments indicate mediated...

We discuss the formation of graded morphogen profiles in a cell layer by nonlinear transport phenomena, important for patterning developing organisms. focus on process termed transcytosis, where results from binding ligands to receptors surface, incorporation into cell, and subsequent externalization. Starting microscopic model, we derive effective equations. show that, contrast extracellular diffusion, transcytosis leads robust ligand which are insensitive rate production.

Antibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we explain these interactions by "translation bottlenecks": points the translation cycle where antibiotics block ribosomal progression. To elucidate underlying mechanisms of drug between inhibitors, generate bottlenecks genetically using inducible control factors regulate well-defined steps. These perturbations accurately mimic antibiotic action interactions, supporting...

Intragenic regions that are removed during maturation of the RNA transcript-introns-are universally present in nuclear genomes eukaryotes1. The budding yeast, an otherwise intron-poor species, preserves two sets ribosomal protein genes differ primarily their introns2,3. Although studies have shed light on role introns under stress and starvation4-6, understanding contribution to ribosome regulation remains challenging. Here, by combining isogrowth profiling7 with single-cell measurements8,...

We present a general theoretical framework to discuss mechanisms of morphogen transport and gradient formation in cell layer. Trafficking events on the cellular scale lead larger scales. particular case transcytosis where morphogens undergo repeated rounds internalization into cells recycling. Based description scale, we derive effective nonlinear equations one two dimensions which are valid analytic expressions for concentration dependence diffusion coefficient degradation rate. effects...