Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Dev Growth Differ. 2023 Apr;65(3):153-160. doi: 10.1111/dgd.12843. Epub 2023 Mar 3.
Neural tissue is derived from three precursor regions: neural plate, neural crest, and preplacodal ectoderm. These regions are determined by morphogen-mediated signaling. Morphogen distribution is generally regulated by binding to an extracellular matrix component, heparan sulfate (HS) proteoglycan. HS is modified by many enzymes, such as N-deacetyl sulfotransferase 1 (Ndst1), which is highly expressed in early development. However, functions of HS modifications in ectodermal patterning are largely unknown. In this study, we analyzed the role of Ndst1 using Xenopus embryos. We found that ndst1 was expressed in anterior neural plate and the trigeminal region at the neurula stage. ndst1 overexpression expanded the neural crest (NC) region, whereas translational inhibition reduced not only the trigeminal region, but also the adjacent NC region, especially the anterior part. At a later stage, ndst1 knocked-down embryos showed defects in cranial ganglion formation. We also found that Ndst1 activates Wnt signaling pathway at the neurula stage. Taken together, our results suggest that N-sulfonated HS accumulates Wnt ligand and activates Wnt signaling in ndst1-expressing cells, but that it inhibits signaling in non-ndst1-expressing cells, leading to proper neuroectodermal patterning.
神经板、神经嵴和颅前腔外胚层。这些区域是由形态发生素介导的信号决定的。形态发生素的分布通常受与其细胞外基质成分硫酸乙酰肝素（HS）蛋白聚糖结合的调节。HS 由许多酶修饰，例如在早期发育中高度表达的 N-去乙酰基磺基转移酶 1（Ndst1）。然而，HS 修饰在外胚层模式形成中的功能在很大程度上是未知的。在这项研究中，我们使用非洲爪蟾胚胎分析了 Ndst1 的作用。我们发现 ndst1 在神经板和神经胚期的三叉神经区域中表达。ndst1 过表达扩大了神经嵴（NC）区域，而翻译抑制不仅减少了三叉神经区域，而且减少了相邻的 NC 区域，特别是前部。在稍后的阶段，ndst1 敲低的胚胎显示颅神经节形成缺陷。我们还发现 Ndst1 在神经胚期激活 Wnt 信号通路。总之，我们的结果表明，N-磺化 HS 在 ndst1 表达细胞中积累 Wnt 配体并激活 Wnt 信号，但在非 ndst1 表达细胞中抑制信号，从而导致适当的神经外胚层模式形成。
