Centre for Developmental Neurobiology, King's College London, Guy's Campus, London, SE1 1UL, UK.
Centre for Biomedical Sciences, Royal Holloway University of London, Egham Hill, Egham, Surrey, TW20 0EX, UK.
Dev Biol. 2020 Apr 15;460(2):108-114. doi: 10.1016/j.ydbio.2019.12.015. Epub 2019 Dec 25.
Bone morphogenetic protein (BMP) signalling is key to many developmental processes, including early regionalisation of the ectoderm. The neural crest is induced here by a combination of BMP and Wnt signals from nearby tissues with many secreted factors contributing to its initial specification at the neural plate border. Gremlin 1 (Grem1) is a secreted BMP antagonist expressed in the neural crest in Xenopus laevis but its function here is unknown. As well as binding BMPs, Grem1 has been shown to interact with heparan sulfate proteoglycans (HSPGs), a family of cell surface macromolecules that regulate a diverse array of signalling molecules by affecting their availability and mode of action. This study describes the impact of HSPGs on the function of Grem1 in neural crest induction. It shows for the first time that Grem1 is required for neural crest development in a two-step process comprising an early HSPG-independent, followed by a late HSPG-dependent phase.
骨形态发生蛋白（BMP）信号通路是许多发育过程的关键，包括外胚层的早期区域化。神经嵴由来自附近组织的 BMP 和 Wnt 信号的组合诱导，许多分泌因子有助于其在神经板边界的初始特化。Gremlin 1（Grem1）是一种在非洲爪蟾中表达的分泌型 BMP 拮抗剂，但它在神经嵴中的功能尚不清楚。除了与 BMP 结合外，Grem1 还被证明与硫酸乙酰肝素蛋白聚糖（HSPG）相互作用，HSPG 是细胞表面大分子家族，通过影响信号分子的可用性和作用方式来调节多种信号分子。本研究描述了 HSPG 对 Grem1 在神经嵴诱导中的功能的影响。它首次表明，Grem1 在神经嵴发育中需要经过两步过程，包括早期 HSPG 非依赖性，随后是晚期 HSPG 依赖性阶段。
