DNA Methyltransferase 3b Is Dispensable for Mouse Neural Crest Development

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.

DNA methyltransferase 3B regulates duration of neural crest production via repression of Sox10

“…A recent study in mice using neural crest-specific conditional deletion of DNMT3B failed to detect obvious defects in neural crest migration or differentiation into craniofacial and cardiac structures (21). One possible explanation for the difference from our results is that the neural crest defect in DNMT3B mutant mice may be related to a requirement for this protein before Wnt1-driven cre expression or in neighboring cell types.…”

Involvement of DNMT3B in the pathogenesis of Hirschsprung disease and its possible role as a regulator of neurogenesis in the human enteric nervous system

“…The migratory NCCs flow occurs with neuronal differentiation in order to achieve a proper ENS development. Although DNMT3B has been reported to be inessential for the development of mouse cranial NCCs, 34 it seems to have a role in the neurogenesis of enteric NCCs. DNMT3B is detected within a narrow window during early neurogenesis, whereas DNMT3A is present in both embryonic and postnatal central nervous system tissue.…”

“…Experimental approaches in different animal models using DNA microarray techniques to profile gene expression in the developing ENS 31,32 have allowed researchers to better understand the cellular and molecular bases of ENS development. 33,34 However, new approaches are still needed for studying the early stages of neurogenesis in the human embryo. Human enteric precursors have become a powerful tool for studying early embryonic stages of gut development.…”

Establishing neural crest identity: a gene regulatory recipe

“…Mutations in DNMT3B seem to be linked to human craniofacial defects present in carriers of the ICF syndrome (Jin et al, 2008), and there is evidence for a role of this regulator in craniofacial development in zebrafish (Rai et al, 2010). However, conditional knockout of Dnmt3b in the mouse neural crest does not cause an obvious neural crest-related phenotype (Jacques-Fricke et al, 2012). Thus, there might be species-specific differences in the function of the enzyme.…”