Zebrafish otolith biomineralization requires polyketide synthase

Kevin D. Thiessen, Steven J. Grzegorski, Yvonne Chin, Lisa N. Higuchi, Christopher J. Wilkinson, Jordan A. Shavit, Ken Kramer

Research output: Contribution to journalArticle

Abstract

Deflecting biomineralized crystals attached to vestibular hair cells are necessary for maintaining balance. Zebrafish (Danio rerio) are useful organisms to study these biomineralized crystals called otoliths, as many required genes are homologous to human otoconial development. We sought to identify and characterize the causative gene in a trio of homozygous recessive mutants, no content (nco) and corkscrew (csr), and vanished (vns), which fail to develop otoliths during early ear development. We show that nco, csr, and vns have potentially deleterious mutations in polyketide synthase (pks1), a multi-modular protein that has been previously implicated in biomineralization events in chordates and echinoderms. We found that Otoconin-90 (Oc90) expression within the otocyst is diffuse in nco and csr; therefore, it is not sufficient for otolith biomineralization in zebrafish. Similarly, normal localization of Otogelin, a protein required for otolith tethering in the otolithic membrane, is not sufficient for Oc90 attachment. Furthermore, eNOS signaling and Endothelin-1 signaling were the most up- and down-regulated pathways during otolith agenesis in nco, respectively. Our results demonstrate distinct processes for otolith nucleation and biomineralization in vertebrates and will be a starting point for models that are independent of Oc90-mediated seeding. This study will serve as a basis for investigating the role of eNOS signaling and Endothelin-1 signaling during otolith formation.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalMechanisms of Development
Volume157
DOIs
StatePublished - Jun 1 2019

Fingerprint

Polyketide Synthases
Otolithic Membrane
Zebrafish
Endothelin-1
Vestibular Hair Cells
Chordata
Human Development
Genes
Ear
Vertebrates
Proteins
Mutation

All Science Journal Classification (ASJC) codes

  • Embryology
  • Developmental Biology

Cite this

Thiessen, K. D., Grzegorski, S. J., Chin, Y., Higuchi, L. N., Wilkinson, C. J., Shavit, J. A., & Kramer, K. (2019). Zebrafish otolith biomineralization requires polyketide synthase. Mechanisms of Development, 157, 1-9. https://doi.org/10.1016/j.mod.2019.04.001

Zebrafish otolith biomineralization requires polyketide synthase. / Thiessen, Kevin D.; Grzegorski, Steven J.; Chin, Yvonne; Higuchi, Lisa N.; Wilkinson, Christopher J.; Shavit, Jordan A.; Kramer, Ken.

In: Mechanisms of Development, Vol. 157, 01.06.2019, p. 1-9.

Research output: Contribution to journalArticle

Thiessen, KD, Grzegorski, SJ, Chin, Y, Higuchi, LN, Wilkinson, CJ, Shavit, JA & Kramer, K 2019, 'Zebrafish otolith biomineralization requires polyketide synthase', Mechanisms of Development, vol. 157, pp. 1-9. https://doi.org/10.1016/j.mod.2019.04.001
Thiessen KD, Grzegorski SJ, Chin Y, Higuchi LN, Wilkinson CJ, Shavit JA et al. Zebrafish otolith biomineralization requires polyketide synthase. Mechanisms of Development. 2019 Jun 1;157:1-9. https://doi.org/10.1016/j.mod.2019.04.001
Thiessen, Kevin D. ; Grzegorski, Steven J. ; Chin, Yvonne ; Higuchi, Lisa N. ; Wilkinson, Christopher J. ; Shavit, Jordan A. ; Kramer, Ken. / Zebrafish otolith biomineralization requires polyketide synthase. In: Mechanisms of Development. 2019 ; Vol. 157. pp. 1-9.
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