Endo Yukinori, Osumi Noriko, Wakamatsu Yoshio
Center for Translational and Advanced Animal Research on Human Diseases, Division of Developmental Neuroscience, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Dev Growth Differ. 2003 Jun;45(3):241-8. doi: 10.1046/j.1524-4725.2003.693.x.
NOTCH signaling plays a key role in cell fate determination in both vertebrates and invertebrates. It is well known that Su(H)/RBP-J is a major mediator of NOTCH signaling. In a previous study, it was shown that NOTCH signaling was involved in cranial neural crest formation in avian embryos. However, Su(H)/RBP-J activity did not appear to be required in this process. In this study, the Deltex/Dtx gene was focussed on as a potential mediator of NOTCH signaling in neural crest formation. At the time of neural crest formation, quail Deltex2 was expressed throughout the ectoderm. Misexpression of a dominant-negative form of Deltex in the ectoderm caused reduced expression of Slug, a neural crest marker. Dominant-negative Deltex expression reduced the expression of Bmp4, a neural crest inducer, whereas co-transfection of Bmp4 with dominant-negative Deltex rescued Slug expression. In parallel, Hairy2 expression in the epidermis was regulated by a Su(H)-dependent pathway. These results indicate that NOTCH signaling has dual functions mediated by either Su(H) or Deltex in the avian embryonic ectoderm.
NOTCH信号通路在脊椎动物和无脊椎动物的细胞命运决定中都起着关键作用。众所周知,Su(H)/RBP-J是NOTCH信号通路的主要介导因子。在先前的一项研究中,已表明NOTCH信号通路参与了鸟类胚胎的颅神经嵴形成。然而,在此过程中似乎并不需要Su(H)/RBP-J的活性。在本研究中,Deltex/Dtx基因被作为神经嵴形成过程中NOTCH信号通路的潜在介导因子进行研究。在神经嵴形成时,鹌鹑的Deltex2在外胚层中全程表达。在外胚层中过表达显性负性形式的Deltex会导致神经嵴标志物Slug的表达降低。显性负性Deltex的表达降低了神经嵴诱导因子Bmp4的表达,而将Bmp4与显性负性Deltex共转染可挽救Slug的表达。同时,表皮中的Hairy2表达受一条依赖于Su(H)的信号通路调控。这些结果表明,在鸟类胚胎外胚层中,NOTCH信号通路具有由Su(H)或Deltex介导的双重功能。