Wang Guang, Li Yan, Wang Xiao-Yu, Chuai Manli, Yeuk-Hon Chan John, Lei Jian, Münsterberg Andrea, Lee Kenneth Ka Ho, Yang Xuesong
Department of Histology and Embryology, School of Medicine, Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou 510632, China.
Division of Cell and Developmental Biology, University of Dundee, Dundee DD1 5EH, United Kingdom.
Mol Biol Cell. 2015 Mar 1;26(5):978-92. doi: 10.1091/mbc.E14-06-1144. Epub 2015 Jan 7.
The brain and reproductive expression (BRE) gene is expressed in numerous adult tissues and especially in the nervous and reproductive systems. However, little is known about BRE expression in the developing embryo or about its role in embryonic development. In this study, we used in situ hybridization to reveal the spatiotemporal expression pattern for BRE in chick embryo during development. To determine the importance of BRE in neurogenesis, we overexpressed BRE and also silenced BRE expression specifically in the neural tube. We established that overexpressing BRE in the neural tube indirectly accelerated Pax7(+) somite development and directly increased HNK-1(+) neural crest cell (NCC) migration and TuJ-1(+) neurite outgrowth. These altered morphogenetic processes were associated with changes in the cell cycle of NCCs and neural tube cells. The inverse effect was obtained when BRE expression was silenced in the neural tube. We also determined that BMP4 and Shh expression in the neural tube was affected by misexpression of BRE. This provides a possible mechanism for how altering BRE expression was able to affect somitogenesis, neurogenesis, and NCC migration. In summary, our results demonstrate that BRE plays an important role in regulating neurogenesis and indirectly somite differentiation during early chick embryo development.
脑与生殖表达(BRE)基因在众多成年组织中表达,尤其在神经和生殖系统中。然而,关于BRE基因在发育中的胚胎中的表达情况及其在胚胎发育中的作用却知之甚少。在本研究中,我们利用原位杂交技术揭示了BRE基因在鸡胚发育过程中的时空表达模式。为了确定BRE基因在神经发生中的重要性,我们过表达了BRE基因,并特异性地沉默了神经管中的BRE基因表达。我们发现,在神经管中过表达BRE基因可间接加速Pax7(+)体节的发育,并直接增加HNK-1(+)神经嵴细胞(NCC)的迁移以及TuJ-1(+)神经突的生长。这些形态发生过程的改变与NCC和神经管细胞的细胞周期变化有关。当在神经管中沉默BRE基因表达时,会产生相反的效果。我们还确定,BRE基因的错误表达会影响神经管中BMP4和Shh的表达。这为改变BRE基因表达如何影响体节发生、神经发生和NCC迁移提供了一种可能的机制。总之,我们的结果表明,BRE基因在早期鸡胚发育过程中对调节神经发生和间接调节体节分化起着重要作用。