Angiotensinogen-, angiotensin-converting enzyme-, and angiotensin II (Ang II) type 1 receptor (AT 1 R)-deficient mice exhibit a dilated renal pelvis (hydronephrosis) and a small papilla. These abnormalities have been attributed to impaired development of the ureteral and pelvic smooth muscle. Defects in the growth and branching of the ureteric bud (UB), which gives rise to the collecting system, have not been examined carefully. This study tested the hypothesis that Ang II stimulates UB growth and branching in the intact metanephros. Immunohistochemistry demonstrated that embryonic mouse kidneys express AT 1 R in the UB and its branches. Embryonic day 11.5 metanephroi were microdissected from Hoxb7-green fluorescence protein mice and grown for 48 h in serum T he metanephros develops via reciprocal inductive interactions between the ureteric bud (UB) and the metanephrogenic mesenchyme (MM) (1,2). Signals from the MM induce UB outgrowth from the nephric duct and its elongation and entrance into the mesenchyme followed by repetitive branching to form the renal collecting system (ureter, pelvis, calyces, and collecting ducts). In turn, emerging UB tips induce surrounding mesenchymal cells to condense, aggregate, undergo mesenchymal-to-epithelial transition, and form nephrons (from the glomerulus to the distal tubule). Therefore, UB branching morphogenesis is critical in determining nephron number, and subtle defects in the efficiency and/or accuracy of this process potentially can have profound effects on the proper development of the metanephric kidney. Decreased nephron endowment is linked to hypertension and eventual progression to chronic renal failure (3,4). In addition, aberrant UB branching morphogenesis causes renal dysplasia, the leading cause of chronic renal failure in human infants.Genetic inactivation of the renin-angiotensin system (RAS) genes in mice causes abnormalities in the development of the ureter, renal pelvis, and papilla (5-9). Angiotensinogen-, angiotensin-converting enzyme (ACE)-, or angiotensin II (Ang II) type 1 receptor (AT 1 R)-deficient mice exhibit pelvic dilation (hydronephrosis) and a small papilla mimicking urinary tract obstruction. Elegant studies from Ichikawa's laboratory have suggested that absence of AT 1 R signaling in ureteral smooth muscle cells impairs pelvic-ureteral smooth muscle development and peristalsis (9). Mutations in the AT 2 R gene in mice and humans are associated with increased incidence of lower urinary tract anomalies, including double ureters and vesicoureteral reflux (10). These findings indicate that UB growth and development are a target for Ang II actions. Work that has performed by several laboratories, including ours, has revealed that the fetal kidney expresses a local RAS. Quantitative analysis of murine Ang II receptors AT 1 R and AT 2 R gene expression indicate that AT 1 R undergo a progressive increase during fetal and neonatal life, whereas AT 2 R are high in the fetus and decline significantly with maturation (11). Immunolocalization studies d...

Gene-targeting studies in mice demonstrate that the renin-angiotensin system is required for the proper development of the renal medulla. In the absence of angiotensin II (ANG II) or the ANG II type 1 (AT1) receptor, mice exhibit poor papillary development and a severe urinary-concentrating defect. These findings imply that the ureteric bud (UB) and its branches are targets for ANG II actions during renal development. However, direct evidence linking ANG II with UB-branching morphogenesis does not exist. Using immunohistochemistry, we demonstrated that UB-derived epithelia express angiotensinogen (Ao) and the AT1 receptor during murine metanephrogenesis. Ao and AT1 receptors are expressed in the UB branches and to a lesser extent in the stromal mesenchyme. AT1 receptor expression in UB-derived epithelia increased from embryo day 12 to day 16 and was observed on both luminal and basolateral membranes. In accord with these findings, cultured murine UB cells express AT1 receptor protein and mRNA. Treatment of UB cells cultured in three-dimensional type I collagen gels with ANG II (10-7 to 10-5 M) elicits a dose-related increase in the number of cells that have primary and secondary branches. These effects of ANG II on UB branching are abrogated by pretreatment with the AT1 receptor antagonist candesartan. These data demonstrate a direct and independent role for ANG II acting via AT1 receptors on UB cell branching in vitro. The presence of Ao in the stroma and AT1 on UB cells supports the notion that cross talk between stroma and epithelial cells is crucial to epithelial branching morphogenesis in the developing kidney.

Synthetic elicitors are drug-like compounds that are structurally distinct from natural defense elicitors. They can protect plants from diseases by activating host immune responses and can serve as tools for the dissection of the plant immune system as well as leads for the development of environmentally-safe pesticide alternatives. By high-throughput screening, we previously identified 114 synthetic elicitors that activate expression of the pathogen-responsive CaBP22−333::GUS reporter gene in Arabidopsis thaliana (Arabidopsis), 33 of which are [(phenylimino)methyl]phenol (PMP) derivatives or PMP-related compounds. Here we report on the characterization of one of these compounds, 2,4-dichloro-6-{(E)-[(3-methoxyphenyl)imino]methyl}phenol (DPMP). DPMP strongly triggers disease resistance of Arabidopsis against bacterial and oomycete pathogens. By mRNA-seq analysis we found transcriptional profiles triggered by DPMP to resemble typical defense-related responses.

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Dubbed as a “global destroyer of crops”, the soil-borne fungus Macrophomina phaseolina (Mp) infects more than 500 plant species including many economically important cash crops. Host defenses against infection by this pathogen are poorly understood. We established interactions between Mp and Arabidopsis thaliana (Arabidopsis) as a model system to quantitatively assess host factors affecting the outcome of Mp infections. Using agar plate-based infection assays with different Arabidopsis genotypes, we found signaling mechanisms dependent on the plant hormones ethylene, jasmonic acid and salicylic acid to control host defense against this pathogen. By profiling host transcripts in Mp-infected roots of the wild-type Arabidopsis accession Col-0 and ein2/jar1, an ethylene/jasmonic acid-signaling deficient mutant that exhibits enhanced susceptibility to this pathogen, we identified hundreds of genes potentially contributing to a diverse array of defense responses, which seem coordinated by complex interplay between multiple hormonal response-pathways. Our results establish Mp/Arabidopsis interactions as a useful model pathosystem, allowing for application of the vast genomics-related resources of this versatile model plant to the systematic investigation of previously understudied host defenses against a major crop plant pathogen.