miR395 is a general component of the sulfate assimilation regulatory network in Arabidopsis

In plants, microRNAs play an important role in many regulatory circuits, including responses to environmental cues such as nutrient limitations. One such microRNA is miR395, which is strongly up-regulated by sulfate deficiency and targets two components of the sulfate uptake and assimilation pathway. Here we show that miR395 levels are affected by treatments with metabolites regulating sulfate assimilation. The precursor of cysteine, O-acetylserine, which accumulates during sulfate deficiency, causes increase in miR395 accumulation. Feeding plants with cysteine, which inhibits sulfate uptake and assimilation, induces miR395 levels while buthionine sulfoximine, an inhibitor of glutathione synthesis, lowers miR395 expression. Thus, miR395 is an integral part of the regulatory network of sulfate assimilation.     

AtZFP1, encoding Arabidopsis thaliana C2H2 zinc-finger protein 1, is expressed downstream of photomorphogenic activation

C₂H₂ zinc-finger proteins play important roles in plant development including floral organogenesis, leaf initiation, lateral shoot initiation, gametogenesis and seed development. The gene for one such protein from Arabidopsis, AtZFP1 (Arabidopsis thalianazinc-finger protein 1), is expressed at high levels in the shoot apex, including the apical meristem, developing leaves and the developing vascular system. In light-grown seedlings, AtZFP1 expression is induced about three days after germination, before the expansion of the true leaves. Dark-grown plants, in which photomorphogenesis is repressed, have no detectable AtZFP1 expression in the shoot apex. Under conditions which induce or mimic photomorphogenic development including growth in the light, shifting dark-grown plants to continuous light or growth on cytokinin in the dark, high levels of AtZFP1 expression are detected. Furthermore, AtZFP1 expression does not depend on active photosynthesis as shown by analysis of plants grown on the carotenoid biosynthetic inhibitor norflurazon. These results are discussed in relation to a possible role for AtZFP1 in shoot development, downstream of photomorphogenic activation.     

The POU domain gene, XlPOU 2 is an essential downstream determinant of neural induction

Bone morphogenetic protein 1 (BMP1) is a metalloprotease that ventralises dorsal mesoderm when overexpressed in early Xenopus embryos. Here we show that Xenopus BMP1 blocks the dorsalising activity of chordin, but not noggin or DeltaxBMPR, when coexpressed in the ventral marginal zone and degrades chordin protein in vitro. We also show that a dominant-negative mutation for XBMP1 (dnBMP1) dorsalises ventral mesoderm in vivo, and blocks degradation of chordin by both XBMP1 and Xolloid, a closely related Xenopus metalloprotease, in vitro. dnBMP1 does not dorsalise ventral mesoderm in UV-irradiated embryos, demonstrating that this activity is dependent upon a functional organiser--the natural source of chordin in Xenopus gastrulae. Our results suggest that XBMP1 may regulate the availability of chordin during vertebrate embryogenesis.     

Proximal tubule haptoglobin gene activation is an integral component of the acute kidney injury "stress response"

Haptoglobin (Hp) synthesis occurs almost exclusively in liver, and it is rapidly upregulated in response to stress. Because many of the pathways that initiate hepatic Hp synthesis are also operative during acute kidney injury (AKI), we tested whether AKI activates the renal cortical Hp gene. CD-1 mice were subjected to six diverse AKI models: ischemia-reperfusion, glycerol injection, cisplatin nephrotoxicity, myoglobinuria, endotoxemia, and bilateral ureteral obstruction. Renal cortical Hp gene induction was determined either 4-72 h or 1-3 wk later by measuring Hp mRNA and protein levels. Relative renal vs. hepatic Hp gene induction during endotoxemia was also assessed. Each form of AKI induced striking and sustained Hp mRNA increases, leading to ～10- to 100-fold renal Hp protein elevations (ELISA; Western blot). Immunohistochemistry, and isolated proximal tubule assessments, indicated that the proximal tubule was the dominant (if not only) site of the renal Hp increases. Corresponding urinary and plasma Hp elevations were surrogate markers of this response. Endotoxemia evoked 25-fold greater Hp mRNA increases in kidney vs. liver, indicating marked renal Hp gene reactivity. Clinical relevance of these findings was suggested by observations that urine samples from 16 patients with established AKI had statistically higher (～12×) urinary Hp levels than urine samples from either normal subjects or from 15 patients with chronic kidney disease. These AKI-associated urinary Hp increases mirrored those seen for urinary neutrophil gelatinase-associated lipoprotein, a well accepted AKI biomarker gene. In summary, these studies provide the first evidence that AKI evokes rapid, marked, and sustained induction of the proximal tubule Hp gene. Hp's known antioxidant, as well as its protean pro- and anti-inflammatory, actions imply potentially diverse effects on the evolution of acute tubular injury.     

Evolution of the bone gene regulatory network

Current fossil, embryological and genetic data shed light on the evolution of the gene regulatory network (GRN) governing bone formation. The key proteins and genes involved in skeletogenesis are well accepted. We discuss when these essential components of the GRN evolved and propose that the Runx genes, master regulators of skeletogenesis, functioned in early cartilages well before they were co-opted to function in the making of bone. Two rounds of whole genome duplication, together with additional tandem gene duplications, created a genetic substrate for segregation of one GRN into several networks regulating the related tissues of cartilage, bone, enamel, and dentin. During this segregation, Runx2 assumed its position at the top of the bone GRN, and Sox9 was excluded from bone, retaining its ancient role in cartilage.