This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Cells in the nervous system use intercellular signaling cues extensively to properly the extend neurites, navigate to and recognize target cells and form and maintain synaptic contacts. The ability to predict secreted proteins from whole genomes has led to the conclusion that perhaps as much as one third of all proteins encoded are secreted into the extracellular space. Given the complexity of nervous systems it stands to reason that many of these secreted proteins act in the patterning of the nervous system. We have generated a library of predicted secreted proteins from the C. elegans genome. We will take a systematic approach using RNA interference (RNAi) to knockdown of all 7,460 predicted secreted proteins and evaluate the effect of this RNAi on multiple aspects of neural development. A preliminary characterization will be done to identify molecules that have an effect on neuronal patterning, and a secondary level quantitative analysis will be done on those molecules. We are using a synthetic lethal screening approach to characterize these molecules first, and then we will examine the outgrowth and synaptic morphology in mutants for genes that demonstrate an effect. Understanding how the nervous system is patterned has long been a goal of neurobiology. A multitude of studies have demonstrated the importance of extracellular proteins on all aspects of neuronal development. The ability to systematically evaluate the effect of loss of function of all secreted proteins has only recently become available. This will provide many novel insights into an extremely complicated part of development.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
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Special Emphasis Panel (ZRR1-RI-4 (01))
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University of Kansas
Anatomy/Cell Biology
Schools of Medicine
Kansas City
United States
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Meneely, Kathleen M; Sundlov, Jesse A; Gulick, Andrew M et al. (2016) An Open and Shut Case: The Interaction of Magnesium with MST Enzymes. J Am Chem Soc 138:9277-93
Oelkers, Peter; Pokhrel, Keshav (2016) Four Acyltransferases Uniquely Contribute to Phospholipid Heterogeneity in Saccharomyces cerevisiae. Lipid Insights 9:31-41
Cautivo, Kelly M; Lizama, Carlos O; Tapia, Pablo J et al. (2016) AGPAT2 is essential for postnatal development and maintenance of white and brown adipose tissue. Mol Metab 5:491-505
Park, Hyewon; Galbraith, Richard; Turner, Thaddeus et al. (2016) Loss of Ewing sarcoma EWS allele promotes tumorigenesis by inducing chromosomal instability in zebrafish. Sci Rep 6:32297
Rider, Virginia; Talbott, Alex; Bhusri, Anuradha et al. (2016) WINGLESS (WNT) signaling is a progesterone target for rat uterine stromal cell proliferation. J Endocrinol 229:197-207
Bellon, Marcia; Lu, Ling; Nicot, Christophe (2016) Constitutive activation of Pim1 kinase is a therapeutic target for adult T-cell leukemia. Blood 127:2439-50
Yao, Li; Li, Yongchao; Knapp, Jennifer et al. (2015) Exploration of molecular pathways mediating electric field-directed Schwann cell migration by RNA-seq. J Cell Physiol 230:1515-24
Merkes, Chris; Turkalo, Timothy K; Wilder, Nicole et al. (2015) Ewing sarcoma ewsa protein regulates chondrogenesis of Meckel's cartilage through modulation of Sox9 in zebrafish. PLoS One 10:e0116627
Vasudevan, Krishna Kumar; Song, Kangkang; Alford, Lea M et al. (2015) FAP206 is a microtubule-docking adapter for ciliary radial spoke 2 and dynein c. Mol Biol Cell 26:696-710
Pope, Michael R; Fleming, Sherry D (2015) TLR2 modulates antibodies required for intestinal ischemia/reperfusion-induced damage and inflammation. J Immunol 194:1190-8

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