Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity.
Bottom Line: Nevertheless, only Sox10 histone H3 lysine 36 dimethylation requires NSD3, revealing unexpected complexity in NSD3-dependent neural crest gene regulation.In addition, by temporally limiting expression of a dominant negative to migratory stages, we identify a novel, direct requirement for NSD3-related methyltransferase activity in neural crest migration.These results identify NSD3 as the first protein methyltransferase essential for neural crest gene expression during specification and show that NSD3-related methyltransferase activity independently regulates migration.
Affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.Show MeSH
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Mentions: To identify the stages when NSD3 is relevant to neural crest development, we defined NSD3 spatiotemporal expression in chick embryos by in situ hybridization. NSD3 transcripts were undetectable until Hamburger and Hamilton (HH; Hamburger and Hamilton, 1951) stage 6, when NSD3 was up-regulated in the neural plate (Figure 1, A and B), preceding the onset of neural crest–specifier gene expression (Khudyakov and Bronner-Fraser, 2009; Betancur et al., 2010). By HH stage 7, NSD3 mRNA was most abundant at rostral neural plate borders (Figure 1, C and D), and within neural tissue, it was restricted to neural folds by 3 somites (HH stage 8–; Figure 1, E and F). At 5 somites (HH stage 8+), NSD3 was strongly expressed in the dorsal neural tube (Figure 1, G and H), which contains neural crest-specifier gene–expressing premigratory neural crest cells (Khudyakov and Bronner-Fraser, 2009). In embryos ranging from 8 (HH stage 9+) to 13 somites (HH stage 11), abundant NSD3 expression persisted in midbrain (Figure 1, I–M) and hindbrain (Figure 1, L and N) migratory neural crest cells that costained for the migratory neural crest cell marker HNK1 (Figure 1K′). Nonneural ectoderm and the otic placode also expressed NSD3. In contrast, related methyltransferases NSD1 and NSD2 were expressed at low, relatively uniform levels throughout early chicken embryos, with only slight enrichment of NSD2 in premigratory and NSD1 in migratory neural crest cells (Supplemental Figure S1). The comparatively abundant, restricted expression of NSD3 in neural crest precursors/cells throughout neural crest specification and migration suggests that NSD3 is the predominant neural crest NSD methyltransferase and could have neural crest–specific developmental functions.
Affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.