Limits...
DNA methyltransferase 3b is dispensable for mouse neural crest development.

Jacques-Fricke BT, Roffers-Agarwal J, Gammill LS - PLoS ONE (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, United States of America.

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.

Show MeSH

Related in: MedlinePlus

Premigratory and migratory neural crest cells express DNMT3b protein.6 somite (s; A) and 10 somite (B) wildtype mouse embryos were harvested, 14 µm transverse frozen sections through the midbrain prepared, and DNMT3b (A, B; A’’, B’’ red) and Sox10 (A’, B’; A’’, B’’ green) protein visualized by immunofluorescence. DNMT3b is abundant in the neural plate, including in Sox10-positive neural crest cells in the neural folds (A; arrowheads). Migratory neural crest cells maintain DNMT3b expression (B, arrowheads). The bright staining at the bottom of the images at both stages is in the foregut.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3475715&req=5

pone-0047794-g001: Premigratory and migratory neural crest cells express DNMT3b protein.6 somite (s; A) and 10 somite (B) wildtype mouse embryos were harvested, 14 µm transverse frozen sections through the midbrain prepared, and DNMT3b (A, B; A’’, B’’ red) and Sox10 (A’, B’; A’’, B’’ green) protein visualized by immunofluorescence. DNMT3b is abundant in the neural plate, including in Sox10-positive neural crest cells in the neural folds (A; arrowheads). Migratory neural crest cells maintain DNMT3b expression (B, arrowheads). The bright staining at the bottom of the images at both stages is in the foregut.

Mentions: While it is known that the neural plate and dorsal spinal cord express DNMT3b [13], [14], [15], and that DNMT3b is upregulated as a consequence of neural crest induction [19], the DNMT3b expression pattern in neural crest cells has not been determined. By immunofluorescence at 6 somites (E8.0), DNMT3b was abundantly expressed by the neural plate and non-neural ectoderm (Fig. 1A). Costaining with the neural crest marker Sox10 (Fig. 1A’) revealed that the DNMT3b-expressing domain included premigratory neural crest cells in the cranial neural folds (Fig. 1A’’; arrowheads). Similarly at 10 somites (E8.5), once cranial neural crest cells were migratory, the neural plate and non-neural ectoderm continued to exhibit strong DNMT3b immunostaining (Fig. 1B). At this stage, DNMT3b (Fig. 1B), Sox10 (Fig. 1B’) double positive (Fig. 1B’’) migratory neural crest cells (arrowheads) were readily apparent migrating through the DNMT3b-negative head mesenchyme. This indicates that premigratory and migratory neural crest cells express DNMT3b.


DNA methyltransferase 3b is dispensable for mouse neural crest development.

Jacques-Fricke BT, Roffers-Agarwal J, Gammill LS - PLoS ONE (2012)

Premigratory and migratory neural crest cells express DNMT3b protein.6 somite (s; A) and 10 somite (B) wildtype mouse embryos were harvested, 14 µm transverse frozen sections through the midbrain prepared, and DNMT3b (A, B; A’’, B’’ red) and Sox10 (A’, B’; A’’, B’’ green) protein visualized by immunofluorescence. DNMT3b is abundant in the neural plate, including in Sox10-positive neural crest cells in the neural folds (A; arrowheads). Migratory neural crest cells maintain DNMT3b expression (B, arrowheads). The bright staining at the bottom of the images at both stages is in the foregut.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475715&req=5

pone-0047794-g001: Premigratory and migratory neural crest cells express DNMT3b protein.6 somite (s; A) and 10 somite (B) wildtype mouse embryos were harvested, 14 µm transverse frozen sections through the midbrain prepared, and DNMT3b (A, B; A’’, B’’ red) and Sox10 (A’, B’; A’’, B’’ green) protein visualized by immunofluorescence. DNMT3b is abundant in the neural plate, including in Sox10-positive neural crest cells in the neural folds (A; arrowheads). Migratory neural crest cells maintain DNMT3b expression (B, arrowheads). The bright staining at the bottom of the images at both stages is in the foregut.
Mentions: While it is known that the neural plate and dorsal spinal cord express DNMT3b [13], [14], [15], and that DNMT3b is upregulated as a consequence of neural crest induction [19], the DNMT3b expression pattern in neural crest cells has not been determined. By immunofluorescence at 6 somites (E8.0), DNMT3b was abundantly expressed by the neural plate and non-neural ectoderm (Fig. 1A). Costaining with the neural crest marker Sox10 (Fig. 1A’) revealed that the DNMT3b-expressing domain included premigratory neural crest cells in the cranial neural folds (Fig. 1A’’; arrowheads). Similarly at 10 somites (E8.5), once cranial neural crest cells were migratory, the neural plate and non-neural ectoderm continued to exhibit strong DNMT3b immunostaining (Fig. 1B). At this stage, DNMT3b (Fig. 1B), Sox10 (Fig. 1B’) double positive (Fig. 1B’’) migratory neural crest cells (arrowheads) were readily apparent migrating through the DNMT3b-negative head mesenchyme. This indicates that premigratory and migratory neural crest cells express DNMT3b.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, United States of America.

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.

Show MeSH
Related in: MedlinePlus