The DBL-1/TGF-β signaling pathway tailors behavioral and molecular host responses to a variety of bacteria in .

Generating specific, robust protective responses to different bacteria is vital for animal survival. Here, we address the role of transforming growth factor β (TGF-β) member DBL-1 in regulating signature host defense responses in to human opportunistic Gram-negative and Gram-positive pathogens. Canonical DBL-1 signaling is required to suppress avoidance behavior in response to Gram-negative, but not Gram-positive bacteria.

Reduced bone morphogenic protein signaling along the gut-neuron axis by heat shock factor promotes longevity.

Aging is a complex and highly regulated process of interwoven signaling mechanisms. As an ancient transcriptional regulator of thermal adaptation and protein homeostasis, the Heat Shock Factor, HSF-1, has evolved functions within the nervous system to control age progression; however, the molecular details and signaling dynamics by which HSF-1 modulates age across tissues remain unclear. Herein, we report a nonautonomous mode of age regulation by HSF-1 in the Caenorhabditis elegans nervous system that works through the bone morphogenic protein, BMP, signaling pathway to modulate membrane trafficking in peripheral tissues.

Small-Scale Extraction of Caenorhabditis elegans Genomic DNA.

Genomic DNA extraction from single or a few Caenorhabditis elegans has many downstream applications, including PCR for genotyping lines, cloning, and sequencing. The traditional proteinase K-based methods for genomic DNA extraction from C. elegans take several hours.

Caenorhabditis elegans saposin-like spp-9 is involved in specific innate immune responses.

Animals counter specific environmental challenges with a combination of broad and tailored host responses. One protein family enlisted in the innate immune response includes the saposin-like antimicrobial proteins. We investigated the expression of a Caenorhabditis elegans saposin-like gene, spp-9, in response to different stresses.

Feedback regulation of BMP signaling by cuticle collagens.

Cellular responsiveness to environment, including changes in extracellular matrix (ECM), is critical for normal processes such as development and wound healing, but can go awry, as in oncogenesis and fibrosis. One type of molecular pathway contributing to this responsiveness is the BMP signaling pathway. Owing to their broad and potent functions, BMPs and their pathways are regulated at multiple levels.

Genetic interactions between the DBL-1/BMP-like pathway and body size-associated genes in .

Bone morphogenetic protein (BMP) signaling pathways control many developmental and homeostatic processes, including cell size and extracellular matrix remodeling. An understanding of how this pathway itself is controlled remains incomplete. To identify novel regulators of BMP signaling, we performed a forward genetic screen in for genes involved in body size regulation, a trait under the control of BMP member DBL-1.

The cisd gene family regulates physiological germline apoptosis through ced-13 and the canonical cell death pathway in Caenorhabditis elegans.

Programmed cell death, which occurs through a conserved core molecular pathway, is important for fundamental developmental and homeostatic processes. The human iron-sulfur binding protein NAF-1/CISD2 binds to Bcl-2 and its disruption in cells leads to an increase in apoptosis. Other members of the CDGSH iron sulfur domain (CISD) family include mitoNEET/CISD1 and Miner2/CISD3.

The Caenorhabditis elegans p38 MAPK Gene plays a key role in protection from mycobacteria.

Mitogen-activated protein kinases (MAPK) are critical mediators of cellular responses to pathogens and are activated in response to infection, but investigation is difficult in multi-cell hosts due to developmental lethality of mutations. Mycobacterium marinum (Mm) is an established model for tuberculosis, a disease afflicting nearly one-third of the world's population. We found that Mm-infected Caenorhabditis elegans display >80% mortality, but nonpathogenic M.

Regulation of extracellular matrix organization by BMP signaling in Caenorhabditis elegans.

In mammals, Bone Morphogenetic Protein (BMP) pathway signaling is important for the growth and homeostasis of extracellular matrix, including basement membrane remodeling, scarring, and bone growth. A conserved BMP member in Caenorhabditis elegans, DBL-1, regulates body length in a dose-sensitive manner. Loss of DBL-1 pathway signaling also results in increased anesthetic sensitivity.

Regulation of TGFβ superfamily signaling by two separable domains of glypican LON-2 in C. elegans.

Regulated intercellular signaling is critical for the normal development and maintenance of multicellular organisms. Glypicans have been shown to regulate signaling by TGFβs, hedgehogs and Wnts, in several cellular contexts. Glypicans comprise a conserved family of heparan sulfated, glycosylphosphatidylinositol (GPI)-linked extracellular proteins.

TGF-β signaling in C. elegans.

Transforming Growth Factor-β (TGF-β) superfamily ligands regulate many aspects of cell identity, function, and survival in multicellular animals. Genes encoding five TGF-β family members are present in the genome of C. elegans.

Two functional domains in C. elegans glypican LON-2 can independently inhibit BMP-like signaling.

Glypicans are multifunctional proteoglycans with regulatory roles in several intercellular signaling pathways. Here, we examine the functional requirements for glypican regulation of bone morphogenetic protein (BMP)-mediated body length in C. elegans.

RNAi screening to identify postembryonic phenotypes in C. elegans.

C. elegans has proven to be a valuable model system for the discovery and functional characterization of many genes and gene pathways. More sophisticated tools and resources for studies in this system are facilitating continued discovery of genes with more subtle phenotypes or roles.

Visualization of Caenorhabditis elegans cuticular structures using the lipophilic vital dye DiI.

The cuticle of C. elegans is a highly resistant structure that surrounds the exterior of the animal(1-4). The cuticle not only protects the animal from the environment, but also determines body shape and plays a role in motility(4-6).

Regulation of genes affecting body size and innate immunity by the DBL-1/BMP-like pathway in Caenorhabditis elegans.

Background: Bone morphogenetic proteins (BMPs) are members of the conserved transforming growth factor beta (TGFbeta superfamily, and play many developmental and homeostatic roles. In C. elegans, a BMP-like pathway, the DBL-1 pathway, controls body size and is involved in innate immunity.

Caenorhabditis elegans SMA-10/LRIG is a conserved transmembrane protein that enhances bone morphogenetic protein signaling.

Bone morphogenetic protein (BMP) pathways control an array of developmental and homeostatic events, and must themselves be exquisitely controlled. Here, we identify Caenorhabditis elegans SMA-10 as a positive extracellular regulator of BMP-like receptor signaling. SMA-10 acts genetically in a BMP-like (Sma/Mab) pathway between the ligand DBL-1 and its receptors SMA-6 and DAF-4.

Glypican LON-2 is a conserved negative regulator of BMP-like signaling in Caenorhabditis elegans.

Bone morphogenetic protein (BMP) pathways are required for a wide variety of developmental and homeostatic decisions, and mutations in signaling components are associated with several diseases. An important aspect of BMP control is the extracellular regulation of these pathways. We show that LON-2 negatively regulates a BMP-like signaling pathway that controls body length in C.

A small issue addressed.

Cell size is an important determinant of body size. While the genetic mechanisms of cell size regulation have been well studied in yeast, this process has only recently been addressed in multicellular organisms. One recent report by Wang et al.

The other side of TGF-beta superfamily signal regulation: thinking outside the cell.

The transforming growth factor beta (TGF-beta) superfamily of paracrine and autocrine signaling molecules regulates a vast array of developmental and homeostatic processes and is itself exquisitely regulated. The misregulation of these molecules often results in cancer and other diseases. Here, we focus on new research that explores how TGF-beta superfamily signaling is controlled between the secreting cell and the target cell.

lon-1 regulates Caenorhabditis elegans body size downstream of the dbl-1 TGF beta signaling pathway.

In Caenorhabditis elegans, two well-characterized TGF beta signaling cascades have been identified: the Small/Male tail abnormal (Sma/Mab) and Dauer formation (Daf) pathways. The Sma/Mab pathway regulates body size morphogenesis and male tail development. The ligand of the pathway, dbl-1, transmits its signal through two receptor serine threonine kinases, daf-4 and sma-6, which in turn regulate the activity of the Smads, sma-2, sma-3, and sma-4.