The development of boundaries between cells and tissues is a critical feature of pattern formation and these same boundaries must be maintained during later adult homeostasis. The mechanisms of boundary establishment and implementation are thus of fundamental biological significance and have profound implications for understanding birth defects as well as cancers, in which boundary constraints are lost, and regeneration, in which boundaries must be formed anew. The goal of this project is to understand the genetic and cellular mechanisms underlying an especially tractable example of boundaries in a post-embryonic vertebrate, the adult pigment stripes of zebrafish. Previous efforts demonstrated that interactions between different classes of pigment cells are essential for stripe development and maintenance, though the particular genes and cell behaviors involved have been elusive.
In Aim 1, innovative hypotheses to explain the specification of stripes and their dynamic reiteration will be tested using mutational and transgenic approaches, cell transplantation and analyses of a naturally occurring pattern variant.
In Aim 2, efforts will focus on mechanisms of subsequent pat- tern implementation, testing roles for specific cellular behaviors and signaling pathways in refining a striped pattern once it has been established, and how these factors have changed to generate a pattern that lacks stripes. These studies will provide valuable new insights into pigment cell boundary formation, with relevance to human health and development, and promise to shed light on the logic of boundary forming mechanisms more generally.

Public Health Relevance

The proposed research is relevant to public health because it focuses on a fundamental aspect of vertebrate development-the establishment and maintenance of boundaries between cell types-that has critical implications for our understanding of pattern formation as well as adult homeostasis and growth control. These studies have potential translational relevance because pigment cells and their neural crest progenitors are associated with a variety of congenital and acquired disorders including malignant melanoma.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM096906-05S1
Application #
9273884
Study Section
Program Officer
Hoodbhoy, Tanya
Project Start
2011-09-15
Project End
2019-08-31
Budget Start
2015-09-01
Budget End
2016-08-31
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Washington
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Spiewak, Jessica E; Bain, Emily J; Liu, Jin et al. (2018) Evolution of Endothelin signaling and diversification of adult pigment pattern in Danio fishes. PLoS Genet 14:e1007538
Eom, Dae Seok; Parichy, David M (2017) A macrophage relay for long-distance signaling during postembryonic tissue remodeling. Science 355:1317-1320
Woodcock, M Ryan; Vaughn-Wolfe, Jennifer; Elias, Alexandra et al. (2017) Identification of Mutant Genes and Introgressed Tiger Salamander DNA in the Laboratory Axolotl, Ambystoma mexicanum. Sci Rep 7:6
Eom, Dae Seok; Bain, Emily J; Patterson, Larissa B et al. (2015) Long-distance communication by specialized cellular projections during pigment pattern development and evolution. Elife 4:
Parichy, David M; Spiewak, Jessica E (2015) Origins of adult pigmentation: diversity in pigment stem cell lineages and implications for pattern evolution. Pigment Cell Melanoma Res 28:31-50
Parichy, David M (2015) Advancing biology through a deeper understanding of zebrafish ecology and evolution. Elife 4:
Inoue, Shinya; Kondo, Shigeru; Parichy, David M et al. (2014) Tetraspanin 3c requirement for pigment cell interactions and boundary formation in zebrafish adult pigment stripes. Pigment Cell Melanoma Res 27:190-200
Patterson, Larissa B; Bain, Emily J; Parichy, David M (2014) Pigment cell interactions and differential xanthophore recruitment underlying zebrafish stripe reiteration and Danio pattern evolution. Nat Commun 5:5299
McMenamin, Sarah K; Bain, Emily J; McCann, Anna E et al. (2014) Thyroid hormone-dependent adult pigment cell lineage and pattern in zebrafish. Science 345:1358-61
Patterson, Larissa B; Parichy, David M (2013) Interactions with iridophores and the tissue environment required for patterning melanophores and xanthophores during zebrafish adult pigment stripe formation. PLoS Genet 9:e1003561

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