Li Yan, Zhang Xiao-Tan, Wang Xiao-Yu, Wang Guang, Chuai Manli, Münsterberg Andrea, Yang Xuesong
Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China; The key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-Sen University, Guangzhou 510080, China.
Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
Exp Cell Res. 2017 Dec 1;361(1):73-84. doi: 10.1016/j.yexcr.2017.10.002. Epub 2017 Oct 5.
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 Robo1 expression. Detection of markers for pre-migratory and migratory neural crest cells, PAX7 and AP-2α, 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 Robo1 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.
Slit/Robo信号通路在胚胎发育过程中对神经元的导向起着重要作用。然而，Slit/Robo信号通路是否以及如何参与颅神经嵴细胞的产生仍不清楚。在本研究中，我们检查了Robo1基因敲除小鼠，以揭示作为颅神经嵴细胞衍生物的小鼠颅额骨和顶骨的发育缺陷。因此，我们在敲低（KD）Robo1表达后，测定了早期鸡胚发育中HNK1颅神经嵴细胞的产生。对迁移前和迁移中的神经嵴细胞标记物PAX7和AP-2α的检测表明，两者的产生均受Robo1基因敲低的影响。此外，我们发现转录因子slug是Robo1基因敲低诱导的颅神经嵴细胞异常分层/上皮-间质转化（EMT）的原因，这也导致E-钙黏蛋白和N-钙黏蛋白表达升高。当在神经管的一半中用显性负性FGFR1阻断FGF信号时，N-钙黏蛋白的表达增强。综上所述，我们表明Slit/Robo信号通路影响颅神经嵴细胞的分层/EMT，而这是颅骨发育所必需的。
