Role of FGFRL1 and other FGF signaling proteins in early kidney development

The mammalian kidney develops from the ureteric bud and the metanephric mesenchyme. In mice, the ureteric bud invades the metanephric mesenchyme at day E10.5 and begins to branch. The tips of the ureteric bud induce the metanephric mesenchyme to condense and form the cap mesenchyme. Some cells of this cap mesenchyme undergo a mesenchymal-to-epithelial transition and differentiate into renal vesicles, which further develop into nephrons. The developing kidney expresses Fibroblast growth factor (Fgf)1, 7, 8, 9, 10, 12 and 20 and Fgf receptors Fgfr1 and Fgfr2. Fgf7 and Fgf10, mainly secreted by the metanephric mesenchyme, bind to Fgfr2b of the ureteric bud and induce branching. Fgfr1 and Fgfr2c are required for formation of the metanephric mesenchyme, however the two receptors can substitute for one another. Fgf8, secreted by renal vesicles, binds to Fgfr1 and supports survival of cells in the nascent nephrons. Fgf9 and Fgf20, expressed in the metanephric mesenchyme, are necessary to maintain survival of progenitor cells in the cortical region of the kidney. FgfrL1 is a novel member of the Fgfr family that lacks the intracellular tyrosine kinase domain. It is expressed in the ureteric bud and all nephrogenic structures. Targeted deletion of FgfrL1 leads to severe kidney dysgenesis due to the lack of renal vesicles. FgfrL1 is known to interact mainly with Fgf8. It is therefore conceivable that FgfrL1 restricts signaling of Fgf8 to the precise location of the nascent nephrons. It might also promote tight adhesion of cells in the condensed metanephric mesenchyme as required for the mesenchymal-to-epithelial transition.

Comparison of the gene expression profiles from normal and Fgfrl1 deficient mouse kidneys reveals downstream targets of Fgfrl1 signaling

Fgfrl1 (fibroblast growth factor receptor-like 1) is a transmembrane receptor that is essential for the development of the metanephric kidney. It is expressed in all nascent nephrogenic structures and in the ureteric bud. Fgfrl1 null mice fail to develop the metanephric kidneys. Mutant kidney rudiments show a dramatic reduction of ureteric branching and a lack of mesenchymal-to-epithelial transition. Here, we compared the expression profiles of wildtype and Fgfrl1 mutant kidneys to identify genes that act downstream of Fgfrl1 signaling during the early steps of nephron formation. We detected 56 differentially expressed transcripts with 2-fold or greater reduction, among them many genes involved in Fgf, Wnt, Bmp, Notch, and Six/Eya/Dach signaling. We validated the microarray data by qPCR and whole-mount in situ hybridization and showed the expression pattern of candidate genes in normal kidneys. Some of these genes might play an important role during early nephron formation. Our study should help to define the minimal set of genes that is required to form a functional nephron.

Search for a heavy narrow resonance decaying to eμ, eτ, or μτ with the ATLAS detector in View the MathML sourcepp collisions at the LHC

This Letter presents the results of a search for a heavy particle decaying into an e(+/-)mu(+/-), e(+/-)tau(+/-), or mu(+/-)tau(+/-) final state in pp collisions at root s = 7 TeV. The data were recorded with the ATLAS detector at the LHC during 2011 and correspond to an integrated luminosity of 4.6 fb(-1). No significant excess above the Standard Model expectation is observed, and exclusions at 95% confidence level are placed on the cross section times branching ratio for the production of an R-parity-violating supersymmetric tau sneutrino. For a sneutrino mass of 500 (2000) GeV, the observed limits on the production cross section times branching ratio are 3.2 (1.4) fb, 42 (17) fb, and 40 (18) fb for the e mu, e tau, and mu tau modes, respectively. These results considerably extend constraints from Tevatron experiments.

Fgfrl1, a fibroblast growth factor receptor-like gene, is found in the cephalochordate Branchiostoma floridae but not in the urochordate Ciona intestinalis

FGFRL1 is a novel member of the fibroblast growth factor receptor family that controls the formation of musculoskeletal tissues. Some vertebrates, including man, cow, dog, mouse, rat and chicken, possess a single copy the FGFRL1 gene. Teleostean fish have two copies, fgfrl1a and fgfrl1b, because they have undergone a whole genome duplication. Vertebrates belong to the chordates, a phylum that also includes the subphyla of the cephalochordates (e.g. Branchiostoma floridae) and urochordates (tunicates, e.g. Ciona intestinalis). We therefore investigated whether other chordates might also possess an FGFRL1 related gene. In fact, a homologous gene was found in B. floridae (amphioxus). The corresponding protein showed 60% sequence identity with the human protein and all sequence motifs identified in the vertebrate proteins were also conserved in amphioxus Fgfrl1. In contrast, the genome of the urochordate C. intestinalis and those from more distantly related invertebrates including the insect Drosophila melanogaster and the nematode Caenorhabditis elegans did not appear to contain any related sequences. Thus, the FGFRL1 gene might have evolved just before branching of the vertebrate lineage from the other chordates.

Neurodegenerative diseases in domestic animals: a comparative review

Neurodegenerative diseases are characterised by selective damage to specific neurons in the nervous system. Interest in such diseases in humans has resulted in considerable progress in the molecular understanding of these disorders in recent decades. Numerous neurodegenerative diseases have also been described in domestic animals but relatively little molecular work has been reported. In the present review, we have classified neurodegenerative disease according to neuroanatomical criteria. We have established two large groups, based on whether the neuronal cell body or its axon was primarily affected. Conditions such as motor neuron diseases, cerebellar degenerations and neuroaxonal dystrophies are discussed in terms of their clinical and neuropathological features. In the most studied disorders, we also present what is known about underlying pathomechanisms, and compare them with their human counterparts. The purpose of this review is to re-kindle interest in this group of diseases and to encourage veterinary researchers to investigate molecular mechanisms by taking advantage of current diagnostic tools.

Genetic relatedness within the genus Campylobacter inferred from rpoB sequences

The genus Campylobacter comprises 17 species, some of which are important animal and human pathogens. To gain more insight into the genetic relatedness of this genus and to improve the molecular tools available for diagnosis, a universal sequencing approach was established for the gene encoding the beta-subunit of RNA polymerase (rpoB) for the genus Campylobacter. A total of 59 strains, including the type strains of currently recognized species as well as field isolates, were investigated in the study. A primer set specific for Campylobacter species enabled straightforward amplification and sequencing of a 530 bp fragment of the rpoB gene. The 16S rRNA gene sequences of all of the strains were determined in parallel. A good congruence was obtained between 16S rRNA and rpoB gene sequence-based trees within the genus Campylobacter. The branching of the rpoB tree was similar to that of the 16S rRNA gene tree, even though a few discrepancies were observed for certain species. The resolution of the rpoB gene within the genus Campylobacter was generally much higher than that of the 16S rRNA gene sequence, resulting in a clear separation of most species and even some subspecies. The universally applicable amplification and sequencing approach for partial rpoB gene sequence determination provides a powerful tool for DNA sequence-based discrimination of Campylobacter species.

Fluorescent microangiography (FMA): an improved tool to visualize the pulmonary microvasculature

Visualization of the complex lung microvasculature and resolution of its three-dimensional architecture remains a difficult experimental challenge. We present a novel fluorescent microscopy technique to visualize both the normal and diseased pulmonary microvasculature. Physiologically relevant pulmonary perfusion conditions were applied using a low-viscosity perfusate infused under continuous airway ventilation. Intensely fluorescent polystyrene microspheres, confined to the vascular space, were imaged through confocal optical sectioning of 200 microm-thick lung sections. We applied this technique to rat lungs and the markedly enhanced depth of field in projected images allowed us to follow vascular branching patterns in both normal lungs and lungs from animals with experimentally induced pulmonary arterial hypertension. In addition, this method allowed complementary immunostaining and identification of cellular components surrounding the blood vessels. Fluorescent microangiography is a widely applicable and quantitative tool for the study of vascular changes in animal models of pulmonary disease.