Robo signaling regulates the production of cranial neural crest cells
Robo signaling regulates the production of cranial neural crest cells
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Robo 信号传导调节颅神经嵴细胞的产生。
DOI：
10.1016/j.yexcr.2017.10.002
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发表时间：
2017-12-01
影响因子：
3.7
通讯作者：
Yang, Xuesong
中科院分区：
文献类型：
--
作者：
Li, Yan;Zhang, Xiao-tan;Yang, Xuesong
Slit/Robo 信号传导在指导胚胎发育中的神经元发育中发挥着重要作用。然而，Slit/Robo 信号是否以及如何参与颅神经嵴细胞的产生仍不清楚。在这项研究中，我们检查了 Robo1 缺陷小鼠，以揭示小鼠颅骨额骨和顶骨的发育缺陷，这些骨是颅神经嵴细胞的衍生物。因此，我们确定了 Robol 表达敲低 (KD) 后鸡胚发育早期 HNK1(+) 颅神经嵴细胞的产生。对迁移前和迁移神经嵴细胞标记物 PAX7 和 AP-2 α 的检测表明，两者的产生均受到 Robo1 KD 的影响。此外，我们发现转录因子slug是Robol KD诱导的颅神经嵴细胞异常分层/EMT的原因，这也导致E-和N-钙粘蛋白的表达升高。当用显性失活 FGFR1 阻断一半神经管中的 FGF 信号传导时，N-钙粘蛋白表达增强。综上所述，我们发现 Slit/Robo 信号传导会影响颅神经嵴细胞的分层/EMT，这是颅骨发育所必需的。
Slit/Robo signaling plays an important role in the guidance of developing neurons in developing embryos. However, it remains obscure whether and how Slit/Robo signaling is involved in the production of cranial neural crest cells. In this study, we examined Robo1 deficient mice to reveal developmental defects of mouse cranial frontal and parietal bones, which are derivatives of cranial neural crest cells. Therefore, we determined the production of HNK1(+) cranial neural crest cells in early chick embryo development after knock-down (KD) of Robol expression. Detection of markers for pre-migratory and migratory neural crest cells, PAX7 and AP-2 alpha, showed that production of both was affected by Robo1 KD. In addition, we found that the transcription factor slug is responsible for the aberrant delamination/EMT of cranial neural crest cells induced by Robol KD, which also led to elevated expression of E- and N-Cadherin. N-Cadherin expression was enhanced when blocking FGF signaling with dominant-negative FGFR1 in half of the neural tube. Taken together, we show that Slit/Robo signaling influences the delamination/EMT of cranial neural crest cells, which is required for cranial bone development.