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Kat2a and Kat2b Acetyltransferase Activity Regulates Craniofacial Cartilage and Bone Differentiation in Zebrafish and Mice.

Authors
  • Sen, Rwik1
  • Pezoa, Sofia A2, 3, 4
  • Carpio Shull, Lomeli5
  • Hernandez-Lagunas, Laura6
  • Niswander, Lee A7, 8
  • Artinger, Kristin Bruk9
  • 1 Department of Craniofacial Biology, School of Dental Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. [email protected]
  • 2 Cell Biology, Stem Cells, and Development Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. [email protected]
  • 3 Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. [email protected]
  • 4 Molecular Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA. [email protected]
  • 5 Department of Craniofacial Biology, School of Dental Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. [email protected]
  • 6 Department of Craniofacial Biology, School of Dental Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. [email protected]
  • 7 Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. [email protected]
  • 8 Molecular Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA. [email protected]
  • 9 Department of Craniofacial Biology, School of Dental Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. [email protected]
Type
Published Article
Journal
Journal of developmental biology
Publication Date
Nov 12, 2018
Volume
6
Issue
4
Identifiers
DOI: 10.3390/jdb6040027
PMID: 30424580
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Cranial neural crest cells undergo cellular growth, patterning, and differentiation within the branchial arches to form cartilage and bone, resulting in a precise pattern of skeletal elements forming the craniofacial skeleton. However, it is unclear how cranial neural crest cells are regulated to give rise to the different shapes and sizes of the bone and cartilage. Epigenetic regulators are good candidates to be involved in this regulation, since they can exert both broad as well as precise control on pattern formation. Here, we investigated the role of the histone acetyltransferases Kat2a and Kat2b in craniofacial development using TALEN/CRISPR/Cas9 mutagenesis in zebrafish and the Kat2ahat/hat (also called Gcn5) allele in mice. kat2a and kat2b are broadly expressed during embryogenesis within the central nervous system and craniofacial region. Single and double kat2a and kat2b zebrafish mutants have an overall shortening and hypoplastic nature of the cartilage elements and disruption of the posterior ceratobranchial cartilages, likely due to smaller domains of expression of both cartilage- and bone-specific markers, including sox9a and col2a1, and runx2a and runx2b, respectively. Similarly, in mice we observe defects in the craniofacial skeleton, including hypoplastic bone and cartilage and altered expression of Runx2 and cartilage markers (Sox9, Col2a1). In addition, we determined that following the loss of Kat2a activity, overall histone 3 lysine 9 (H3K9) acetylation, the main epigenetic target of Kat2a/Kat2b, was decreased. These results suggest that Kat2a and Kat2b are required for growth and differentiation of craniofacial cartilage and bone in both zebrafish and mice by regulating H3K9 acetylation.

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