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首页> 外文期刊>EBioMedicine >Fate Specification of Neural Plate Border by Canonical Wnt Signaling and Grhl3 is Crucial for Neural Tube Closure
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Fate Specification of Neural Plate Border by Canonical Wnt Signaling and Grhl3 is Crucial for Neural Tube Closure

机译：通过规范的Wnt信号和Grhl3的神经板边界的命运规范对于神经管闭合至关重要

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During primary neurulation, the separation of a single-layered ectodermal sheet into the surface ectoderm (SE) and neural tube specifies SE and neural ectoderm (NE) cell fates. The mechanisms underlying fate specification in conjunction with neural tube closure are poorly understood. Here, by comparing expression profiles between SE and NE lineages, we observed that uncommitted progenitor cells, expressing stem cell markers, are present in the neural plate bordereural fold prior to neural tube closure. Our results also demonstrated that canonical Wnt and its antagonists, DKK1/KREMEN1, progressively specify these progenitors into SE or NE fates in accord with the progress of neural tube closure. Additionally, SE specification of the neural plate border via canonical Wnt signaling is directed by the grainyhead-like 3 (Grhl3) transcription factor. Thus, we propose that the fate specification of uncommitted progenitors in the neural plate border by canonical Wnt signaling and its downstream effector Grhl3 is crucial for neural tube closure. This study implicates that failure in critical genetic factors controlling fate specification of progenitor cells in the neural plate bordereural fold coordinated with neural tube closure may be potential causes of human neural tube defects.
机译：在初级护理过程中，将单层外胚层片分离为表面外胚层（SE）和神经管会指定SE和神经外胚层（NE）的细胞命运。命运规范与神经管闭合相关的机制了解甚少。在这里，通过比较SE和NE谱系之间的表达谱，我们观察到在神经管闭合之前，在神经板边界/神经折叠处存在表达干细胞标记的未定型祖细胞。我们的研究结果还表明，经典的Wnt及其拮抗剂DKK1 / KREMEN1随着神经管闭合的进展，逐渐将这些祖细胞指定为SE或NE命运。另外，经由典型的Wnt信号传导的神经板边界的SE规范由粒头状3（Grhl3）转录因子指导。因此，我们建议通过规范的Wnt信号及其下游效应器Grhl3在神经板边界未定祖细胞的命运规范对于神经管闭合至关重要。这项研究表明，在控制神经板边界/神经折叠的前祖细胞命运规范的关键遗传因素中，失败与神经管闭合有关可能是人类神经管缺陷的潜在原因。

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