Novel Mechanisms in Zebrafish Otolith Nucleation, Tethering, and Dysfunction

Deflecting biomineralized crystals attached to mechanosensory hair cells are necessary for maintaining bodily balance. Zebrafish (Danio rerio) are useful organisms to study these biomineralized crystals called otoliths, as many required genes are homologous to human otoconial development. This study examines the underlying mechanisms of zebrafish otolith nucleation, tethering, and dysfunction. Here I show that 1) otolith nucleation is impaired in three zebrafish mutants with mutations in polyketide synthase, 2) otolin-1b is a putative component of the cuticular plate and involved with otolith growth and maintenance, and 3) otolin-1a, a component of the otolithic membrane, could be used to monitor risk for vestibular dysfunction during Benign Paroxysmal Positional Vertigo (BPPV) onset and following microgravity exposure. While previous studies have identified polyketide synthase as a mediator of biomineralization events in chordates and echinoderms, I demonstrate that it is evolutionarily conserved in zebrafish. The role and function of vertebrate Otolin-1 has been expanded by the characterization of hair-cell specific otolin-1b. Finally, I provide the groundwork for future studies on the genetic and environmental factors of vestibular dysfunction. Each one of these processes provides insight into novel mechanisms in otolith formation and maintenance.

Grantor dc:publisher

Creighton University

Year dc:date.issued

2019

Author dc:creator

• Thiessen, Kevin D.

Advisor dc:contributor.advisor

• Kramer, Kenneth

Statement dc:rights

• Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10504/123335

OAI identifier oai:identifier

oai:cdr.creighton.edu:10504/123335