Roles for zebrafish trpm7 in growth, skeletogenesis, kidney function and physiological ion homeostasis

Simple item page
dc.contributor.advisorParichy, David M.en
dc.contributor.committeeMemberWallingford, John B.en
dc.contributor.committeeMemberFischer, Janice A.en
dc.contributor.committeeMemberPaull, Tanya T.en
dc.contributor.committeeMemberShankland, Martyen
dc.creatorElizondo, Michael Reubenen
dc.date.accessioned2010-08-20T19:26:09Zen
dc.date.accessioned2010-08-20T19:26:16Zen
dc.date.accessioned2017-05-11T22:20:04Z
dc.date.available2010-08-20T19:26:09Zen
dc.date.available2010-08-20T19:26:16Zen
dc.date.available2017-05-11T22:20:04Z
dc.date.issued2009-12en
dc.date.submittedDecember 2009en
dc.date.updated2010-08-20T19:26:17Zen
dc.descriptiontexten
dc.description.abstractDevelopment of the adult form requires coordinated growth and patterning of multiple traits in response to local gene activity as well as global endocrine and physiological effectors. In recent years the zebrafish has been utilized as a favorable animal model as a step towards dissecting and better understanding these postembryonic developmental processes. One of the more powerful methods utilized in zebrafish has been the identification of new gene functions through the use of mutant screens. The nutria mutant was recovered from one such screen to identify postembryonic defects in pigment pattern, growth and metamorphosis. These mutants exhibited a pigment cell defect, touch unresponsiveness and severe growth retardation. Here I will discuss my work towards dissecting the underlying developmental processes governing the phenotypic changes in nutria mutants. I characterize gross alterations in skeletal development in nutria mutants that lead to accelerated endochondral ossification but delayed intramembranous ossification. I show that the nutria phenotype results from mutations in trpm7, which encodes a transient receptor potential (TRP) family member that functions as both a cation channel and a kinase. I find trpm7 expression in the fish-specific, ion homeostasis-regulating gland known as the corpuscles of Stannius (CS), and in the mesonephric kidney. I show that mutants also develop kidney stones. Together these results suggest a role for trpm7 activity in regulation of physiological ion homeostasis. Next I confirm that role by identifying late-embryonic and early larval defects in the CS and the kidney, two organs that regulate physiological ion homeostasis. I demonstrate the early larval detection of kidney stones in trpm7 mutants and show that their appearance is presaged by decreased levels of total calcium and magnesium. Furthermore I establish a link between trpm7 function in the CS and stanniocalcin1 (stc1), a potent molecular regulator of calcium homeostasis. Finally, using transgenic overexpression and morpholino-oligonucleotide knockdown, I demonstrate that stc1 modulates calcium and magnesium levels in trpm7 mutant and wild-type backgrounds. Together these analyses establish postembryonic roles for trpm7 function in growth, skeletogenesis, kidney function, and physiological ion homeostasis.en
dc.format.mimetypeapplication/pdfen
dc.identifier.urihttp://hdl.handle.net/2152/ETD-UT-2009-12-544en
dc.language.isoengen
dc.subjecttrpm7en
dc.subjectZebrafishen
dc.subjectDanioen
dc.subjectRerioen
dc.subjectBoneen
dc.subjectKidneyen
dc.subjectGrowthen
dc.subjectIon homeostasisen
dc.subjectCalciumen
dc.subjectMagnesiumen
dc.subjectKidney stoneen
dc.subjectStanniocalcinen
dc.subjectstc1en
dc.subjectSkeletogenesisen
dc.titleRoles for zebrafish trpm7 in growth, skeletogenesis, kidney function and physiological ion homeostasisen
dc.type.genrethesisen

Files

Collections

University of Texas at Austin