Prmt1 regulates craniofacial bone formation upstream of Msx1

Mech Dev. 2018 Aug;152:13-20. doi: 10.1016/j.mod.2018.05.001. Epub 2018 May 1.

Abstract

Protein arginine methylation has been recently identified as an important form of post-translational modification (PTM). It is carried out by the protein arginine methyltransferase (PRMT) family of enzymes, which in mammals consists of nine members. Among them, PRMT1 is the major arginine methyltransferase and participates in transcription, signal transduction, development and cancer. The function of PRMT1 in craniofacial development remains unclear. We generated Wnt1-Cre;Prmt1fl/fl mice with cranial neural crest (CNC)-specific deletion of Prmt1 and compared CNC-derived craniofacial bones from newborn control and Wnt1-Cre;Prmt1fl/fl mice. The size, surface area and volume of the premaxilla, maxilla, palatine bone, frontal bone, and mandible were analyzed using three-dimensional (3D) micro-computed tomography (microCT). We found that Prmt1 deficiency led to alterations in craniofacial bones including the premaxilla, maxilla, palatine bone, frontal bone, and mandible, as well as defects in the incisor and alveolar bone, recapitulating changes seen in Msx1-deficient mice. We further determined that Prmt1 depletion resulted in significant downregulation of Msx1 in calvaria-derived preosteoblast and primordium of frontal bone and mandible. Our study reveals critical roles of PRMT1 in the formation of CNC-derived craniofacial bones and suggests that Prmt1 is an upstream regulator of Msx1 in craniofacial bone development.

MeSH terms

  • Animals
  • Animals, Genetically Modified / genetics
  • Arginine / genetics
  • Bone Development / genetics*
  • Frontal Bone / growth & development
  • Frontal Bone / metabolism
  • Gene Expression Regulation, Developmental
  • Integrases / genetics
  • MSX1 Transcription Factor / deficiency
  • MSX1 Transcription Factor / genetics*
  • Maxilla / growth & development
  • Methylation
  • Mice
  • Protein Processing, Post-Translational / genetics*
  • Protein-Arginine N-Methyltransferases / deficiency
  • Protein-Arginine N-Methyltransferases / genetics*
  • Wnt1 Protein / genetics

Substances

  • MSX1 Transcription Factor
  • Msx1 protein, mouse
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • Arginine
  • Prmt1 protein, mouse
  • Protein-Arginine N-Methyltransferases
  • Cre recombinase
  • Integrases