Kctd15 inhibits neural crest formation by attenuating Wnt/β-catenin signaling output
Kctd15 inhibits neural crest formation by attenuating Wnt/β-catenin signaling output
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DOI：
10.1242/dev.047548
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发表时间：
2010-09-15
期刊：
影响因子：
4.6
通讯作者：
Dawid, Igor B.
中科院分区：
文献类型：
--
作者：
Dutta, Sunit;Dawid, Igor B.
神经嵴（NC）前体是干细胞，在迁移到胚胎的不同位置后能够形成多种细胞类型。 NC 和基板在神经板边界 (NPB) 处形成。 Wnt 通路对于确定该细胞群中 NC 与基板的身份至关重要。在这里，我们描述了含有 BTB 结构域的蛋白钾通道四聚化结构域 15 (Kctd15) 作为 NPB 中表达的因子，可有效抑制斑马鱼和青蛙胚胎中的 NC 诱导。 Kctd15 的过表达会抑制 NC 形成，而 Kctd15 的敲低会导致 NC 结构域的扩展。同样，爪蟾动物外植体中 Wnt3a 加 Chordin 的 NC 诱导被 Kctd15 抑制，但组成型活性 β-catenin 逆转了 Kctd15 介导的 NC 诱导抑制。通过减少 Kctd15 表达来挽救通过抑制 Wnt8.1 来抑制 NC 诱导，从而将 Kctd15 的作用与 Wnt 途径联系起来。我们认为 Kctd15 通过减弱经典 Wnt 通路的输出来抑制 NC 形成，从而限制 NC 结构域超出其正常范围的扩展。
Neural crest (NC) precursors are stem cells that are capable of forming many cell types after migration to different locations in the embryo. NC and placodes form at the neural plate border (NPB). The Wnt pathway is essential for specifying NC versus placodal identity in this cell population. Here we describe the BTB domain-containing protein Potassium channel tetramerization domain containing 15 (Kctd15) as a factor expressed in the NPB that efficiently inhibits NC induction in zebrafish and frog embryos. Whereas overexpression of Kctd15 inhibited NC formation, knockdown of Kctd15 led to expansion of the NC domain. Likewise, NC induction by Wnt3a plus Chordin in Xenopus animal explants was suppressed by Kctd15, but constitutively active beta-catenin reversed Kctd15-mediated suppression of NC induction. Suppression of NC induction by inhibition of Wnt8.1 was rescued by reduction of Kctd15 expression, linking Kctd15 action to the Wnt pathway. We propose that Kctd15 inhibits NC formation by attenuating the output of the canonical Wnt pathway, thereby restricting expansion of the NC domain beyond its normal range.