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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.

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The ventricular septum is intact when cardiac neural crest cells lack functional DNMT3b.E16.5 embryonic hearts from DNMT3b+/fl (wildtype; A, n = 4), DNMT3bfl/− or Sox10-cre; DNMT3b+/fl (heterozygous in neural crest cells; B, n = 8), and either Sox10-cre; DNMT3bfl/− (C, n = 8) or Wnt1-cre; DNMT3bfl/− (homozygous deleted in neural crest cells; D, n = 6) were dissected, paraffin sectioned, and hematoxylin and eosin stained. The neural crest-derived upper, membranous ventricular septum (arrows) formed normally in all genotypes. The aorta (a) and pulmonary artery (p) were also correctly attached and arranged (the aorta and pulmonary artery are not apparent in A due to a tilted plane of section).
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pone-0047794-g005: The ventricular septum is intact when cardiac neural crest cells lack functional DNMT3b.E16.5 embryonic hearts from DNMT3b+/fl (wildtype; A, n = 4), DNMT3bfl/− or Sox10-cre; DNMT3b+/fl (heterozygous in neural crest cells; B, n = 8), and either Sox10-cre; DNMT3bfl/− (C, n = 8) or Wnt1-cre; DNMT3bfl/− (homozygous deleted in neural crest cells; D, n = 6) were dissected, paraffin sectioned, and hematoxylin and eosin stained. The neural crest-derived upper, membranous ventricular septum (arrows) formed normally in all genotypes. The aorta (a) and pulmonary artery (p) were also correctly attached and arranged (the aorta and pulmonary artery are not apparent in A due to a tilted plane of section).

Mentions: Contribution of DNMT3b mutant neural crest cells to the heart did not affect cardiac development. Cardiac neural crest cells form the aorticopulmonary septum that separates the aorta and pulmonary artery, as well as the membranous portion of the ventricular septum [35]. Aberrant cardiac neural crest development therefore results in conotruncal heart malformations [36], like the upper ventricular septal defects observed in DNMT3b mutant embryos [16]. Nevertheless, hematoxylin and eosin stained sections of E16.5 hearts revealed completely enclosed ventricles with no gaps in the ventricular septum in wildtype (Fig. 5A), heterozygous (Fig. 5B) and neural crest mutant animals (Fig. 5C, D, arrowheads). In addition, the aorta and pulmonary artery were distinct and properly attached to the ventricles (Fig. 5 and not shown). Therefore, a heart that includes DNMT3b mutant neural crest cells undergoes proper morphogenesis, and DNMT3b−/− heart defects [16] are not due to a requirement for DNMT3b in cardiac neural crest cells.


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

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

The ventricular septum is intact when cardiac neural crest cells lack functional DNMT3b.E16.5 embryonic hearts from DNMT3b+/fl (wildtype; A, n = 4), DNMT3bfl/− or Sox10-cre; DNMT3b+/fl (heterozygous in neural crest cells; B, n = 8), and either Sox10-cre; DNMT3bfl/− (C, n = 8) or Wnt1-cre; DNMT3bfl/− (homozygous deleted in neural crest cells; D, n = 6) were dissected, paraffin sectioned, and hematoxylin and eosin stained. The neural crest-derived upper, membranous ventricular septum (arrows) formed normally in all genotypes. The aorta (a) and pulmonary artery (p) were also correctly attached and arranged (the aorta and pulmonary artery are not apparent in A due to a tilted plane of section).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3475715&req=5

pone-0047794-g005: The ventricular septum is intact when cardiac neural crest cells lack functional DNMT3b.E16.5 embryonic hearts from DNMT3b+/fl (wildtype; A, n = 4), DNMT3bfl/− or Sox10-cre; DNMT3b+/fl (heterozygous in neural crest cells; B, n = 8), and either Sox10-cre; DNMT3bfl/− (C, n = 8) or Wnt1-cre; DNMT3bfl/− (homozygous deleted in neural crest cells; D, n = 6) were dissected, paraffin sectioned, and hematoxylin and eosin stained. The neural crest-derived upper, membranous ventricular septum (arrows) formed normally in all genotypes. The aorta (a) and pulmonary artery (p) were also correctly attached and arranged (the aorta and pulmonary artery are not apparent in A due to a tilted plane of section).
Mentions: Contribution of DNMT3b mutant neural crest cells to the heart did not affect cardiac development. Cardiac neural crest cells form the aorticopulmonary septum that separates the aorta and pulmonary artery, as well as the membranous portion of the ventricular septum [35]. Aberrant cardiac neural crest development therefore results in conotruncal heart malformations [36], like the upper ventricular septal defects observed in DNMT3b mutant embryos [16]. Nevertheless, hematoxylin and eosin stained sections of E16.5 hearts revealed completely enclosed ventricles with no gaps in the ventricular septum in wildtype (Fig. 5A), heterozygous (Fig. 5B) and neural crest mutant animals (Fig. 5C, D, arrowheads). In addition, the aorta and pulmonary artery were distinct and properly attached to the ventricles (Fig. 5 and not shown). Therefore, a heart that includes DNMT3b mutant neural crest cells undergoes proper morphogenesis, and DNMT3b−/− heart defects [16] are not due to a requirement for DNMT3b in cardiac neural crest cells.

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