For all children to have the opportunity to achieve their full potential for healthy lives, free from disease, it is essential to understand mechanisms underlying developmental patterning and how this patterning can go awry in human disease. The goal of this Program Project is to elucidate one such mechanism - the function of reciprocal intercellular signaling that specifies embryonic cells to traverse particular developmental pathways and express restricted fates. This goal will be achieved for three sets of cell fates in three Component Projects (CPs), using the zebrafish, a widely-utilized animal model organism pioneered by this group at the University of Oregon. The projects take advantage of the attributes of the zebrafish for developmental genetic analyses, including gene expression analyses, genetic mosaic analyses, and loss and gain-of-function experiments that will establish the nature of the interactions. The projects include screens for new mutations and genes important in these signaling pathways, facilitated by the unique Zebrafish Facility, one of five Core Facilities. CP I """"""""Reciprocal signaling in skeletogenesis"""""""" tests hypotheses about the functioning of signaling molecules in patterning the shape of the palatal skeleton and the pathway of chondral bone development. Results will improve understanding of signaling pathways between cranial epithelia and mesenchyme, and between cartilage and bone progenitors. They will thereby inform our understanding of cleft palate, one of the most common human birth defects, and osteoarthritis that will affect nearly one in five Americans during the coming decade. CP II """"""""Reciprocal signaling in synaptogenesis"""""""" tests a novel hypothesis that Usher genes encode proteins that interact in a complex mediating reciprocal signaling between sensory cells and neurons with which the sensory cells form synaptic connections. The analyses will identify the critical components of the Usher gene network and provide an integrated understanding of Usher syndrome, the most frequent cause of deaf blindness. CP III """"""""Reciprocal signaling in gastrointestinal tract development"""""""" explores the hypothesis that gut microbiota influence cell fate decisions in gut epithelium and enteric nervous system by modulating a highly conserved molecular signal, Notch. The work will elucidate reciprocal signaling and how it goes awry in disorders such as inflammatory bowel disease and related disorders that together affect more than 10% of the US population.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
3P01HD022486-23S1
Application #
8051040
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Henken, Deborah B
Project Start
2010-05-01
Project End
2010-09-30
Budget Start
2010-05-01
Budget End
2010-09-30
Support Year
23
Fiscal Year
2010
Total Cost
$47,540
Indirect Cost
Name
University of Oregon
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
948117312
City
Eugene
State
OR
Country
United States
Zip Code
97403
Ferreira, Carlos R; Xia, Zhi-Jie; Clément, Aurélie et al. (2018) A Recurrent De Novo Heterozygous COG4 Substitution Leads to Saul-Wilson Syndrome, Disrupted Vesicular Trafficking, and Altered Proteoglycan Glycosylation. Am J Hum Genet 103:553-567
Logan, Savannah L; Dudley, Christopher; Baker, Ryan P et al. (2018) Automated high-throughput light-sheet fluorescence microscopy of larval zebrafish. PLoS One 13:e0198705
Clément, Aurélie; Blanco-Sánchez, Bernardo; Peirce, Judy L et al. (2018) Cog4 is required for protrusion and extension of the epithelium in the developing semicircular canals. Mech Dev :
Parthasarathy, Raghuveer (2018) Monitoring microbial communities using light sheet fluorescence microscopy. Curr Opin Microbiol 43:31-37
Troll, Joshua V; Hamilton, M Kristina; Abel, Melissa L et al. (2018) Microbiota promote secretory cell determination in the intestinal epithelium by modulating host Notch signaling. Development 145:
Dona, Margo; Slijkerman, Ralph; Lerner, Kimberly et al. (2018) Usherin defects lead to early-onset retinal dysfunction in zebrafish. Exp Eye Res 173:148-159
Blanco-Sánchez, Bernardo; Clément, Aurélie; Fierro Jr, Javier et al. (2018) Grxcr1 Promotes Hair Bundle Development by Destabilizing the Physical Interaction between Harmonin and Sans Usher Syndrome Proteins. Cell Rep 25:1281-1291.e4
Rolig, Annah S; Sweeney, Emily Goers; Kaye, Lila E et al. (2018) A bacterial immunomodulatory protein with lipocalin-like domains facilitates host-bacteria mutualism in larval zebrafish. Elife 7:
Logan, Savannah L; Thomas, Jacob; Yan, Jinyuan et al. (2018) The Vibrio cholerae type VI secretion system can modulate host intestinal mechanics to displace gut bacterial symbionts. Proc Natl Acad Sci U S A 115:E3779-E3787
Ganz, J; Baker, R P; Hamilton, M K et al. (2018) Image velocimetry and spectral analysis enable quantitative characterization of larval zebrafish gut motility. Neurogastroenterol Motil 30:e13351

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