体节发生
中文名称
通路描述
体节是由周期性从发育中的前侧中胚层（Diaz-Cuadros et al. 2020）中切割或分节的间充质界限段。体节形成概念化使用钟和波前沿模型（综述在 Saga 2012）。钟存在于前中胚层细胞中，在允许状态和不可反应状态之间循环，允许状态可以发生分节，而不可反应状态则不能。波前沿沿前中胚层移动，并在遇到处于允许状态的细胞时引起分节，因此体节的尺寸由钟的周期性和波前沿的迁移速度决定。分段过程由 WNY 信号、FGF 信号和特别是 Notch 信号驱动（综述在 Dunwoodie et al. 2009, Ferjentsik et al. 2009），Hubaud 和 Pourquie 2014）。后 - 前向 WNT 和 FGF 信号梯度的交点和前 - 后向视黄酸信号梯度的交点调节体节边界的位置，任何梯度的扰动都会影响体节边界（综述在 Gibb et al. 2010, Hubard 和 Pourquie et al. 2014）。因此 WNT、FGF 和视黄酸似乎形成波前沿，也称为决定前沿。分段周期性由 Notch 途径中 HES7 介导的负反馈循环控制，这些构成了分子振荡器或分段钟（Bessho et al. 2003）。Notch 激活 LFNG 表达和 LFNG 抑制 Notch 信号（可能通过调节 DLL3 配体），这构成了另一个作为分子振荡器的负反馈循环（Dale et al. 2003, Falk et al. 2022）。钟振荡在原始 streak 中新生前中胚层（Falk et al. 2022）中启动，并向前中胚层传递后 - 前向波以调节 MESP2/RIPPLY2 表达以启动分段。MESP2 激活 EPHA4（Nakajima et al. 2006），一种参与段边界形成的 Eph 受体。MESP2 还激活 RIPPLY2（Morimoto et al. 2007），一种 TBX6 的抑制剂（Zhao et al. 2018）。TBX6 是 MESP2 的激活剂，因此 MESP2 间接通过 RIPPLY2 抑制其自身表达。分段钟组件（例如 DLL3、MESP2、LFNG 和 HES7）的突变导致人类先天性脊柱缺陷（Dunwoodie et al. 2009, Nóbrega et al. 2021）。
英文描述
Somitogenesis Somites are bounded segments of mesenchyme that are periodically cleaved, or segmented, from the developing anterior paraxial mesoderm (Diaz-Cuadros et al. 2020). Somite formation is conceptualized using a clock and wavefront model (reviewed in Saga 2012). The clock is present in cells of the presomitic mesoderm and cycles between a permissive state in which segmentation can occur and a refractory state in which it cannot. The wavefront moves along the presomitic mesoderm and causes segmentation where and when it encounters cells in the permissive state, thus the size of the somites is determined by the periodicity of the clock and the migration speed of the wavefront.
The segmentation process is driven by WNY signaling, FGF signaling, and especially the Notch signaling (reviewed in Dunwoodie et al. 2009, Ferjentsik et al. 2009), Hubaud and Pourquie 2014). The intersection of posterior-anterior gradients of WNT and FGF signaling and an anterior-posterior gradient of retinoic acid signaling regulates the position of somite boundaries as perturbation of any of the gradients affects somite boundaries (reviewed in Gibb et al. 2010, Hubard and Pourquie et al. 2014). Thus WNT, FGF, and retinoic acid appear to form the wavefront, also called the determination front. Segmentation periodicity is controlled by HES7-mediated negative feedback loops in the Notch pathway, which constitute a molecular oscillator or segmentation clock (Bessho et al. 2003). Activation of LFNG expression by Notch and inhibition of Notch signaling by LFNG, possibly via regulation of the DLL3 ligand (Bochter et al. 2022), constitute another negative feedback loop that acts as a molecular oscillator (Dale et al. 2003, Falk et al. 2022). Clock oscillations are initiated in nascent presomitic mesoderm in the primitive streak of the gastrulating embryo (Falk et al. 2022) and posterior-to-anterior waves sweep to anterior paraxial mesoderm to regulate MESP2/RIPPLY2 expression to initiate segmentation. MESP2 activates expression of EPHA4 (Nakajima et al. 2006), an Eph receptor that participates in segment boundary formation. MESP2 also activates expression of RIPPLY2 (Morimoto et al. 2007), an inhibitor of TBX6 (Zhao et al. 2018). TBX6 is an activator of MESP2, therefore MESP2 indirectly inhibits its own expression via RIPPLY2.
Mutations in components of the segmentation clock, for example DLL3, MESP2, LFNG, and HES7, cause congenital vertebral defects in humans (Dunwoodie et al. 2009, Nóbrega et al. 2021).
The segmentation process is driven by WNY signaling, FGF signaling, and especially the Notch signaling (reviewed in Dunwoodie et al. 2009, Ferjentsik et al. 2009), Hubaud and Pourquie 2014). The intersection of posterior-anterior gradients of WNT and FGF signaling and an anterior-posterior gradient of retinoic acid signaling regulates the position of somite boundaries as perturbation of any of the gradients affects somite boundaries (reviewed in Gibb et al. 2010, Hubard and Pourquie et al. 2014). Thus WNT, FGF, and retinoic acid appear to form the wavefront, also called the determination front. Segmentation periodicity is controlled by HES7-mediated negative feedback loops in the Notch pathway, which constitute a molecular oscillator or segmentation clock (Bessho et al. 2003). Activation of LFNG expression by Notch and inhibition of Notch signaling by LFNG, possibly via regulation of the DLL3 ligand (Bochter et al. 2022), constitute another negative feedback loop that acts as a molecular oscillator (Dale et al. 2003, Falk et al. 2022). Clock oscillations are initiated in nascent presomitic mesoderm in the primitive streak of the gastrulating embryo (Falk et al. 2022) and posterior-to-anterior waves sweep to anterior paraxial mesoderm to regulate MESP2/RIPPLY2 expression to initiate segmentation. MESP2 activates expression of EPHA4 (Nakajima et al. 2006), an Eph receptor that participates in segment boundary formation. MESP2 also activates expression of RIPPLY2 (Morimoto et al. 2007), an inhibitor of TBX6 (Zhao et al. 2018). TBX6 is an activator of MESP2, therefore MESP2 indirectly inhibits its own expression via RIPPLY2.
Mutations in components of the segmentation clock, for example DLL3, MESP2, LFNG, and HES7, cause congenital vertebral defects in humans (Dunwoodie et al. 2009, Nóbrega et al. 2021).
所含基因
45 个基因