During vertebrate development, the embryo is subdivided into domains that correlate with eventual specializations in cellular function. The regional expression and function of multiple transcription factors, acting antagonistically and in concert, define unique identities for these domains. Complex interactions among these transcription factors regulate cellular and molecular events that are unique to each tissue. Discovering how positional control of genetic networks leads to cellular form and function is an important step towards understanding the mechanisms underlying human birth defects and disease. The investigators collaborating in this program project have a history of common scientific interests and approaches, all using the zebrafish, a vertebrate model organism particularly suited to genetic, molecular, and embryonic manipulations. The three interrelated component projects will address a common theme: how do particular regulatory genes act to control region-specific cell differentiation? All three projects share a common focus on the roles of transcription factors, especially members of the T-box protein family, asking: what are the required roles of these genes? How is their expression controlled? And, how do combinations of transcription factors act together to regulate downstream effector genes that execute position-specific functions? Each project will study the patterning of a different tissue: the mesoderm germ layer;Kupffer's vesicle, a source of left-right patterning;and the dorsal retina. Comparing results among these systems will allow us to search for general principles by which transcription factors or effector genes act together, as well as to ask whether specific molecular interactions are common to different tissues. In addition to this intellectual synergy, this application will provide common resources to allow cooperation on large-scale experiments that were impossible for each group alone. A Zebrafish Genetics Core Facility will house existing wild-type and mutant fish, generate animals for genetic screens, and provide resources for phenotype analyses. A Molecular Analysis Core Facility will perform sequence-based screening of mutagenized genomes (TILLING), genotyping of identified mutants, and gene expression analysis by semi-automated in situ hybridization. Through interactions between the projects and using the core units, this program will identify new components of the molecular pathways that regulate fundamental steps in vertebrate tissue patterning, discover effector genes that allow cells to express position-specific fates and behaviors, and start to dissect the genetic networks that control positional identity during development.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Program Projects (P01)
Project #
Application #
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Coulombe, James N
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Utah
Schools of Medicine
Salt Lake City
United States
Zip Code
Morrow, Zachary T; Maxwell, Adrienne M; Hoshijima, Kazuyuki et al. (2017) tbx6l and tbx16 are redundantly required for posterior paraxial mesoderm formation during zebrafish embryogenesis. Dev Dyn 246:759-769
Yabe, Taijiro; Hoshijima, Kazuyuki; Yamamoto, Takashi et al. (2016) Quadruple zebrafish mutant reveals different roles of Mesp genes in somite segmentation between mouse and zebrafish. Development 143:2842-52
Ota, Satoshi; Hisano, Yu; Muraki, Michiko et al. (2013) Efficient identification of TALEN-mediated genome modifications using heteroduplex mobility assays. Genes Cells 18:450-8
Kruse-Bend, Renee; Rosenthal, Jude; Quist, Tyler S et al. (2012) Extraocular ectoderm triggers dorsal retinal fate during optic vesicle evagination in zebrafish. Dev Biol 371:57-65
Xing, Lingyan; Hoshijima, Kazuyuki; Grunwald, David J et al. (2012) Zebrafish foxP2 zinc finger nuclease mutant has normal axon pathfinding. PLoS One 7:e43968
Dahlem, Timothy J; Hoshijima, Kazuyuki; Jurynec, Michael J et al. (2012) Simple methods for generating and detecting locus-specific mutations induced with TALENs in the zebrafish genome. PLoS Genet 8:e1002861
Bisgrove, Brent W; Makova, Svetlana; Yost, H Joseph et al. (2012) RFX2 is essential in the ciliated organ of asymmetry and an RFX2 transgene identifies a population of ciliated cells sufficient for fluid flow. Dev Biol 363:166-78
Wang, Xu; Kopinke, Daniel; Lin, Junji et al. (2012) Wnt signaling regulates postembryonic hypothalamic progenitor differentiation. Dev Cell 23:624-36
Demarest, Bradley L; Horsley, Wyatt H; Locke, Erin E et al. (2011) Trans-centromere effects on meiotic recombination in the zebrafish. Genetics 187:333-6
Wythe, Joshua D; Jurynec, Michael J; Urness, Lisa D et al. (2011) Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish. Dis Model Mech 4:607-21

Showing the most recent 10 out of 13 publications