DNA methyltransferase 3b is dispensable for mouse neural crest development

PLoS One. 2012;7(10):e47794. doi: 10.1371/journal.pone.0047794. Epub 2012 Oct 18.

Abstract

The neural crest is a population of multipotent cells that migrates extensively throughout vertebrate embryos to form diverse structures. Mice mutant for the de novo DNA methyltransferase DNMT3b exhibit defects in two neural crest derivatives, the craniofacial skeleton and cardiac ventricular septum, suggesting that DNMT3b activity is necessary for neural crest development. Nevertheless, the requirement for DNMT3b specifically in neural crest cells, as opposed to interacting cell types, has not been determined. Using a conditional DNMT3b allele crossed to the neural crest cre drivers Wnt1-cre and Sox10-cre, neural crest DNMT3b mutants were generated. In both neural crest-specific and fully DNMT3b-mutant embryos, cranial neural crest cells exhibited only subtle migration defects, with increased numbers of dispersed cells trailing organized streams in the head. In spite of this, the resulting cranial ganglia, craniofacial skeleton, and heart developed normally when neural crest cells lacked DNMT3b. This indicates that DNTM3b is not necessary in cranial neural crest cells for their development. We conclude that defects in neural crest derivatives in DNMT3b mutant mice reflect a requirement for DNMT3b in lineages such as the branchial arch mesendoderm or the cardiac mesoderm that interact with neural crest cells during formation of these structures.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basal Ganglia / embryology
  • Basal Ganglia / enzymology
  • Branchial Region / embryology
  • Branchial Region / enzymology
  • Cell Differentiation
  • Cell Movement
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental*
  • Heart / embryology
  • Integrases / genetics
  • Integrases / metabolism
  • Mesoderm / embryology
  • Mesoderm / enzymology
  • Mice
  • Mice, Transgenic
  • Mutation
  • Neural Crest / embryology
  • Neural Crest / enzymology*
  • Neurogenesis / genetics*
  • SOXE Transcription Factors / genetics
  • SOXE Transcription Factors / metabolism
  • Skull / embryology
  • Skull / enzymology
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism

Substances

  • SOXE Transcription Factors
  • Sox10 protein, mouse
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA methyltransferase 3B
  • Cre recombinase
  • Integrases

Grant support

This research was supported by American Cancer Society grant #IRG-58-001-49-IRG32 (LSG), and National Institutes of Health Individual Ruth L. Kirschstein National Research Service Awards F32 DE021651 (BJF) and F32 DE019973 (JRA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.