Asymmetric inheritance of the apical domain and self-renewal of retinal ganglion cell progenitors depend on Anillin function.

Divisions that generate one neuronal lineage-committed and one self-renewing cell maintain the balance of proliferation and differentiation for the generation of neuronal diversity. The asymmetric inheritance of apical domains and components of the cell division machinery has been implicated in this process, and might involve interactions with cell fate determinants in regulatory feedback loops of an as yet unknown nature. Here, we report the dynamics of Anillin - an essential F-actin regulator and furrow component - and its contribution to progenitor cell divisions in the developing zebrafish retina. We find that asymmetrically dividing retinal ganglion cell progenitors position the Anillin-rich midbody at the apical domain of the differentiating daughter. anillin hypomorphic conditions disrupt asymmetric apical domain inheritance and affect daughter cell fate. Consequently, the retinal cell type composition is profoundly affected, such that the ganglion cell layer is dramatically expanded. This study provides the first in vivo evidence for the requirement of Anillin during asymmetric neurogenic divisions. It also provides insights into a reciprocal regulation between Anillin and the ganglion cell fate determinant Ath5, suggesting a mechanism whereby the balance of proliferation and differentiation is accomplished during progenitor cell divisions in vivo.journal articleresearch support, non-u.s. gov't2015 Mar 012015 02 05importe

Divergent <i>Wnt8a</i> Gene Expression in Teleosts

<div><p>The analysis of genes in evolutionarily distant but morphologically similar species is of major importance to unravel the changes in genomes over millions of years, which led to gene silencing and functional diversification. We report the analysis of <i>Wnt8a</i> gene expression in the medakafish and provide a detailed comparison to other vertebrates. In all teleosts analyzed there are two paralogous <i>Wnt8a</i> copies. These show largely overlapping expression in the early developing zebrafish embryo, an evolutionarily distant relative of medaka. In contrast to zebrafish, we find that both maternal and zygotic expression of particularly one <i>Wnt8a</i> paralog has diverged in medaka. While <i>Wnt8a1</i> expression is mostly conserved at early embryonic stages, the expression of <i>Wnt8a2</i> differs markedly. In addition, both genes are distinctly expressed during organogenesis unlike the zebrafish homologs, which may hint at the emergence of functional diversification of <i>Wnt8a</i> ligands during evolution.</p></div

Phylogenetic analysis of <i>Wnt8a</i> genes.

<p>The medaka genome contains two <i>Wnt8a</i> genes (bold). The <i>Wnt8a</i> cDNA sequence alignment of various species shows that the medaka paralogous copies cluster well with those of evolutionarily related teleosts. acul., aculeatus; nigro., nigroviridis.</p

Sites of <i>Wnt8a</i> gene expression in medaka, zebrafish, Xenopus and mouse.

<p><i>Wnt8.1</i> and <i>Wnt8.2</i> correspond to zebrafish <i>Wnt8a ORF1</i> and <i>Wnt8a ORF2</i>, respectively.</p>*<p>, very transient; **, hindgut; +, expressed by in situ hybridisation; −, not expressed by in situ hybridisation. Abbreviations: cht, chaudal haematopoietic tissue; n.a., not applicable; n.r., not reported.</p

<i>Wnt8a</i> gene paralog expression pattern differ during somitogenesis and organogenesis.

<p>(A,B,E,G–I) Dorsal and (C,D,F) lateral views with anterior to the left, (A–F) focused on the tail region. (A,B) At 38 hours post fertilization (hpf), <i>Wnt8a1</i> transcripts are found in the axial part of the tailbud including the posterior end of the notochord (arrow), while <i>Wnt8a2</i> is widely expressed in the tailbud, presomitic mesoderm and developing somites. (C–F) <i>Wnt8a1</i> expressing cells are found in the tailbud at 2,5 days post fertilization (dpf) and 3,5 dpf and <i>Wnt8a2</i> is expressed in caudal hematopoietic tissue (arrows in D). Line in (F) marks the position of the transversal section shown in the inset. (G) After 4 dpf, <i>Wnt8a1</i> is expressed in the entire gut, oesophagus (not before 4 dpf (I)), swim- and gall bladder. The anatomy of these structures has been well described previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085303#pone.0085303-Kobayashi1" target="_blank">[40]</a>. (I) The dissected gut system is shown for clarity. The inset shows <i>Wnt8a1</i> expression in the outflow tract of the dissected heart. (H) <i>Wnt8a2</i> transcripts are present in the otic vesicles. a, atrium; ca, caudal artery; cv, caudal vein; g, gall bladder; l, liver; no, notochord; nt, neural tube; oe, oesophagus; oft, outflow tract; ov, otic vesicle; psm, presomitic mesoderm; sb, swim bladder; som, somites; tb, tailbud; v, ventricle.</p

Ceratapion basicorne (Illiger) (Coleoptera: Curculionidae): biosaggi di laboratorio e campo per valutarne la specificità fisiologica come agente di controllo di Centaurea solstitialis l. (Asteraceae: Cardueae)

Ceratapion basicorne (Illiger) (Coleoptera: Curculionidae): laboratory and open field trials to assess its specificity as biocontrol agent of Centaurea solstitialis (Asteraceae: Cardueae). Prospective biological control agents generally must be demonstrated to not pose risks to non-target plants. Laboratory experiments evaluating host plant specificity are the most common method of evaluating such risk; however, they are constrained by limitations of space and number of replicates, giving sometimes unclear results. Field experiments in the land of origin of the prospective agent can provide more realistic conditions. The root boring weevil Ceratapion basicorne normally oviposits in the leaves of young yellow starthistle (Centaurea solstitialis) plants, and larvae develop inside the root crown and pupate inside the plant. Despite the high specificity showed for the target weed by the weevil, during its screening as biological control agent for yellow starthistle, a permit application to release it in the U.S.A. was denied in 2006 because of the risk it could be dangerous to safflower (Carthamus tinctorius): in fact, this weevil, has been reported to develop occasionally on the non-target plant in laboratory no-choice experiments. The main concern was related to the economic importance of safflower, hypothesizing that the number of replicate plants in the previous experiments was still too small. When a small risk is perceived for a very abundant plant, such as a crop, larger scale experiments are needed to improve confidence in the results. For this reason, an additional open field test was set up in Rome, releasing adults of C. basicorne in a field experiment in which two varieties of safflower were grown in solid blocks near a small number of yellow starthistle plants. The weevil infested 54% of the yellow starthistle plants, while no individuals of C. basicorne were reared from 1021 safflower plants. Additional testing could not reduce this probability to zero; however, the consistency of results from field experiments in three countries and the absence of any report of this insect being reared from safflower in the field support the conclusion that this weevil species poses no significant risk to safflower

HIGH-RESOLUTION PHARMACOGENETIC PROFILES OF GENES INVOLVED IN DRUG ABSORPTION, DISTRIBUTION, METABOLISM AND ELIMINATION IN ADULT PHILADELPHIA-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS

Background: Inter-individual variations in genes encoding drug metabolizing enzymes and transporters have been demonstrated to influence the response to therapy. However so far, how these genetic variations interact to produce specific drug related phenotypes in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) has not yet been investigated. Aim: In order to investigate potential genetic structure and related pharmacogenetic profiles, around 2000 variants in more than 200 genes involved in drug absorption, distribution, metabolism and elimination were genotyped and studied with a population genetics approach in 45 Ph+ ALL patients. Methods: The Drug Metabolizing Enzymes and Transporters (DMET™, Affymetrix) platform, covering more than 90% of the most biologically relevant drug absorption, distribution, metabolism and excretion (ADME) markers was used for successfully genotyping 1931 variants in Ph+ ALL patients treated with the tyrosine kinase inhibitor Dasatinib. A model-based clustering method for inferring population structure using genotype data was applied by means of the Structure software assuming a model in which there are K populations - each one of them being characterized by a set of allele frequencies at each locus - to which individuals are probabilistically assigned according to their genotypes. Distribution of the genetic variance observed among the identified leukemia sub-groups was investigated with a locus by locus Analysis of the Molecular Variance (AMOVA) by means of the Arlequin 3.01 package, exploiting information on genotypes allelic content and frequencies. Results: Three different sub-groups (G1, G2, G3), made up of 2, 12 and 31 patients respectively, were identified in the examined ALL sample, according to their different patterns of allele frequency. A statistical support for this finding was provided by AMOVA results which pointed out a substantial level of genetic differentiation among G1 and the other two sub-groups (Fst = 0.099, p0.3) and significant Fst values; whereas a total of 50 loci, located on the NAT2, VKORC1, CYP4F2, CYP2B6, UGT2B7 and CYP2D6 genes, showed moderate to high (>0.08) significant Fst values in the G2/G3 comparison. Conclusions: Differences of allele frequencies observed among the identified ALL sub-groups prove that an evident genetic structure is detectable in our sample by genotyping loci involved in drug metabolism. Supported by: Fondazione GIMEMA Onlus, European LeukemiaNet, AIL, AIRC, Fondazione Del Monte di Bologna e Ravenna, FIRB 2006, Ateneo RFO grants, Project of integreted program (PIO), Programma di Ricerca Regione – Università 2007 – 2009