The broad role of Nkx3.2 in the development of the zebrafish axial skeleton

PLoS One. 2021 Aug 19;16(8):e0255953. doi: 10.1371/journal.pone.0255953. eCollection 2021.

Abstract

The transcription factor Nkx3.2 (Bapx1) is an important chondrocyte maturation inhibitor. Previous Nkx3.2 knockdown and overexpression studies in non-mammalian gnathostomes have focused on its role in primary jaw joint development, while the function of this gene in broader skeletal development is not fully described. We generated a mutant allele of nkx3.2 in zebrafish with CRISPR/Cas9 and applied a range of techniques to characterize skeletal phenotypes at developmental stages from larva to adult, revealing loss of the jaw joint, fusions in bones of the occiput, morphological changes in the Weberian apparatus, and the loss or deformation of bony elements derived from basiventral cartilages of the vertebrae. Axial phenotypes are reminiscent of Nkx3.2 knockout in mammals, suggesting that the function of this gene in axial skeletal development is ancestral to osteichthyans. Our results highlight the broad role of nkx3.2 in zebrafish skeletal development and its context-specific functions in different skeletal elements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone and Bones
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins*
  • Transcription Factors
  • Zebrafish*

Substances

  • Homeodomain Proteins
  • Transcription Factors

Grants and funding

TH received a grant from Swedish Research Council (Vetenskapsrådet), grant number 621-2012-4673. https://www.vr.se/ AA received grant from SciLifeLab Uppsala for the development of the OPT system and a Technology Development grant from SciLifeLab. https://www.scilifelab.se/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.