In recent years, the development and implementation of animal-free approaches to chemical and pharmaceutical hazard and risk assessment has taken off. Alternative approaches are being developed starting from the perspective of human biology and physiology.

Neural tube closure is a vital step that occurs early in human development. Correct closure of the neural tube depends on a complex interplay between proteins along a number of protein concentration gradients. The sensitivity of neural tube closure to chemical disturbance of signalling pathways such as the retinoid pathway, is well known. To map the pathways underlying neural tube closure, literature data on the molecular regulation of neural tube closure were collected. As the process of neural tube closure is highly conserved in vertebrates, the extensive literature available for the mouse was used whilst considering its relevance for humans. Thus, important cell compartments, regulatory pathways, and protein interactions essential for neural tube closure under physiological circumstances were identified and mapped. An understanding of aberrant processes leading to neural tube defects (NTDs) requires detailed maps of neural tube embryology, including the complex genetic signals and responses underlying critical cellular dynamical and biomechanical processes. The retinoid signaling pathway serves as a case study for this ontology because of well-defined crosstalk with the genetic control of neural tube patterning and morphogenesis. It is a known target for mechanistically-diverse chemical structures that disrupt neural tube closure

The data presented in this manuscript will set the stage for constructing mathematical models and computer simulation of neural tube closure for human-relevant AOPs and predictive toxicology.

近年来，化学和药物危害和风险评估的无动物方法的开发和实施已经开始。从人类生物学和生理学的角度出发，正在开发替代方法。

神经管闭合是人类发育早期发生的重要步骤。神经管的正确闭合取决于蛋白质之间沿着许多蛋白质浓度梯度的复杂相互作用。神经管闭合对信号通路（如类视黄醇通路）的化学干扰的敏感性是众所周知的。为了绘制神经管闭合的潜在通路，收集了关于神经管闭合分子调节的文献数据。由于神经管闭合过程在脊椎动物中高度保守，因此在考虑其与人类的相关性的同时，使用了可用于小鼠的大量文献。因此，确定并绘制了重要的细胞区室、调节通路和生理环境下神经管闭合所必需的蛋白质相互作用。了解导致神经管缺陷 (NTD) 的异常过程需要详细的神经管胚胎学图谱，包括复杂的遗传信号和关键细胞动力学和生物力学过程背后的反应。由于与神经管模式和形态发生的遗传控制明确定义的串扰，视黄醇信号通路作为该本体的案例研究。它是破坏神经管闭合的机械多样化化学结构的已知目标 由于与神经管模式和形态发生的遗传控制明确定义的串扰，视黄醇信号通路作为该本体的案例研究。它是破坏神经管闭合的机械多样化化学结构的已知目标 由于与神经管模式和形态发生的遗传控制明确定义的串扰，视黄醇信号通路作为该本体的案例研究。它是破坏神经管闭合的机械多样化化学结构的已知目标

本手稿中提供的数据将为构建与人类相关的 AOP 和预测毒理学的神经管闭合数学模型和计算机模拟奠定基础。