Abstract:
:Neural crest stem cells arise within the central nervous system but then undergo an epithelial-to-mesenchymal transition to migrate away and contribute to the peripheral nervous system and craniofacial skeleton. Here we show that DNA methyltransferase 3B (DNMT3B) is responsible for the loss of competence of dorsal neural tube cells to generate emigrating neural crest cells. DNMT3B knockdown results in up-regulation of neural crest markers, prolonged neural crest emigration, and subsequent precocious neuronal differentiation of the trigeminal ganglion. We find that DNMT3B binds to the promoter of Sox10, known to be important for neural crest emigration and lineage acquisition. Bisulfite sequencing further reveals methylation of the Sox10 promoter region upon cessation of emigration in normal embryos, whereas this mark is reduced after DNMT3B loss. Taken together, these results reveal the importance of DNA methylation in regulating the ability of neural tube cells to produce neural crest cells and the timing of peripheral neuron differentiation.
journal_name
Proc Natl Acad Sci U S Aauthors
Hu N,Strobl-Mazzulla PH,Simoes-Costa M,Sánchez-Vásquez E,Bronner MEdoi
10.1073/pnas.1318408111subject
Has Abstractpub_date
2014-12-16 00:00:00pages
17911-6issue
50eissn
0027-8424issn
1091-6490pii
1318408111journal_volume
111pub_type
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