Kctd15 通过减弱 Wnt/β-catenin 信号输出抑制神经嵴形成。
Kctd15 inhibits neural crest formation by attenuating Wnt/beta-catenin signaling output.
机构信息
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Development. 2010 Sep;137(18):3013-8. doi: 10.1242/dev.047548. Epub 2010 Aug 4.
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.
神经嵴（NC）前体细胞是能够在迁移到胚胎的不同位置后形成多种细胞类型的干细胞。NC 和基板在神经板边界（NPB）处形成。Wnt 途径对于在该细胞群中指定 NC 与基板身份是必不可少的。在这里，我们将含有 BTB 结构域的蛋白钾通道四聚体结构域包含 15 个（Kctd15）描述为在 NPB 中表达的因子，该因子有效地抑制斑马鱼和青蛙胚胎中的 NC 诱导。虽然 Kctd15 的过表达抑制了 NC 的形成，但 Kctd15 的敲低导致 NC 域的扩张。同样，Wnt3a 和 Chordin 在非洲爪蟾动物外植体中的 NC 诱导被 Kctd15 抑制，但组成型活性 β-catenin 逆转了 Kctd15 对 NC 诱导的抑制作用。通过抑制 Wnt8.1 抑制 NC 诱导被降低 Kctd15 表达所挽救，将 Kctd15 作用与 Wnt 途径联系起来。我们提出 Kctd15 通过减弱经典 Wnt 途径的输出来抑制 NC 的形成，从而限制 NC 域的扩张超出其正常范围。
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