The vertebrate genome contains a predicted 30,000+ genes, most of unknown function. The annotation of genes is one of the major next steps in understanding the vertebrate genome. The recent development of morpholino-based gene 'knockdown' technology in zebrafish has opened the door to the genome-wide assignment of function based on sequence in a model vertebrate. In this competitive renewal, we will focus on the systematic assignment of biological function to 300 putative secreted proteins to identify new players in these clinically relevant processes. We will accomplish this goal through the following specific aims:
Aim I. Development of a secreted protein morpholino core database. Morpholinos targeted to these genes will be generated and examined for function in the following biological processes:
Aim II. Isolation of secreted proteins required for embryonic patterning and organogenesis.
Aim III. Isolation of secreted proteins required for cardiovascular and sensory organ formation.
Aim I V. Isolation of secreted proteins required for digestive organ formation and function.
Aim V. Annotation of the identified phenotypes and incorporation of this gene set information into the international zebrafish database at ZFIN. The identification of molecules required for vertebrate patterning and organ function has critical implications for the understanding of genetic deficiencies in these processes. In addition, the molecules identified as crucial for development in vivo will serve as key substrate molecules for potential small molecule drug target intervention and for the establishment of conditions for stem cell manipulation such as in vitro organ formation. The zebrafish offers the first opportunity for a comprehensive analysis of these processes using as template an entire vertebrate genome.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM063904-06
Application #
7115678
Study Section
Genome Study Section (GNM)
Program Officer
Haynes, Susan R
Project Start
2001-09-01
Project End
2007-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
6
Fiscal Year
2006
Total Cost
$512,748
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Genetics
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Pogoda, Hans-Martin; Riedl-Quinkertz, Iris; Löhr, Heiko et al. (2018) Direct activation of chordoblasts by retinoic acid is required for segmented centra mineralization during zebrafish spine development. Development 145:
Richardson, Rebecca; Hammerschmidt, Matthias (2018) The role of Rho kinase (Rock) in re-epithelialization of adult zebrafish skin wounds. Small GTPases 9:230-236
Löhr, Heiko; Hess, Simon; Pereira, Mafalda M A et al. (2018) Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit. Cell Rep 23:1728-1741
Sæle, Øystein; Rød, Kari Elin L; Quinlivan, Vanessa H et al. (2018) A novel system to quantify intestinal lipid digestion and transport. Biochim Biophys Acta Mol Cell Biol Lipids 1863:948-957
Anderson, Jennifer L; Mulligan, Timothy S; Shen, Meng-Chieh et al. (2017) mRNA processing in mutant zebrafish lines generated by chemical and CRISPR-mediated mutagenesis produces unexpected transcripts that escape nonsense-mediated decay. PLoS Genet 13:e1007105
Wang, Lei; Ma, Xiao; Xu, Xiaolei et al. (2017) Systematic identification and characterization of cardiac long intergenic noncoding RNAs in zebrafish. Sci Rep 7:1250
Stainier, Didier Y R; Raz, Erez; Lawson, Nathan D et al. (2017) Guidelines for morpholino use in zebrafish. PLoS Genet 13:e1007000
El-Rass, Suzan; Eisa-Beygi, Shahram; Khong, Edbert et al. (2017) Disruption ofpdgfraalters endocardial and myocardial fusion during zebrafish cardiac assembly. Biol Open 6:348-357
Otis, Jessica P; Shen, Meng-Chieh; Quinlivan, Vanessa et al. (2017) Intestinal epithelial cell caveolin 1 regulates fatty acid and lipoprotein cholesterol plasma levels. Dis Model Mech 10:283-295
Quinlivan, Vanessa H; Wilson, Meredith H; Ruzicka, Josef et al. (2017) An HPLC-CAD/fluorescence lipidomics platform using fluorescent fatty acids as metabolic tracers. J Lipid Res 58:1008-1020

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