Lawrence N, Langdon T, Brennan K, Arias A M
Department of Zoology, University of Cambridge, CB2 3EJ, Cambridge, United Kingdom.
Curr Biol. 2001 Mar 20;11(6):375-85. doi: 10.1016/s0960-9822(01)00120-8.
Members of the Notch family of receptors mediate a process known as lateral inhibition that plays a prominent role in the suppression of cell fates during development. This function is triggered by a ligand, Delta, and is implemented by the release of the intracellular domain of Notch from the membrane and by its interaction with the protein Suppressor of Hairless [Su(H)] in the nucleus. There is evidence that Notch can also signal independently of Su(H). In particular, in Drosophila, there is evidence that a Su(H)-independent activity of Notch is associated with Wingless signaling.
We report that Ubx(VM)B, a visceral mesoderm-specific enhancer of the Ubx gene of Drosophila, is sensitive to Notch signaling. In the absence of Notch, but not of Su(H), the enhancer becomes activated earlier and over a wider domain than in the wild type. Furthermore, the removal of Notch reduces the requirement for Disheveled-mediated Wingless signaling to activate this enhancer. This response to Notch is likely to be mediated by the dTcf binding sites in the Ubx(VM)B enhancer.
Our results show that, in Drosophila, an activity of Notch that is likely to be independent of Su(H) inhibits Wingless signaling on Ubx(VM)B. A possible target of this activity is dTcf. As dTcf has been shown to be capable of repressing Wingless targets, our results suggest that this repressive activity may be regulated by Notch. Finally, we suggest that Wingless signaling is composed of two steps, a down-regulation of a Su(H)-independent Notch activity that modulates the activity of dTcf and a canonical Wingless signaling event that regulates the activity of Armadillo and its interaction with dTcf.
Notch受体家族成员介导一种称为侧向抑制的过程,该过程在发育过程中对细胞命运的抑制起着重要作用。此功能由配体Delta触发,并通过Notch细胞内结构域从膜上释放以及其与细胞核中无翅蛋白抑制因子[Su(H)]的相互作用来实现。有证据表明,Notch也可以独立于Su(H)进行信号传导。特别是在果蝇中,有证据表明Notch的一种不依赖Su(H)的活性与Wingless信号传导有关。
我们报道,果蝇Ubx基因的内脏中胚层特异性增强子Ubx(VM)B对Notch信号敏感。在没有Notch但有Su(H)的情况下,该增强子比野生型更早且在更广泛的区域被激活。此外,去除Notch会降低激活该增强子对Disheveled介导的Wingless信号传导的需求。对Notch的这种反应可能由Ubx(VM)B增强子中的dTcf结合位点介导。
我们的结果表明,在果蝇中,一种可能独立于Su(H)的Notch活性抑制了Ubx(VM)B上的Wingless信号传导。这种活性的一个可能靶点是dTcf。由于已证明dTcf能够抑制Wingless靶点,我们的结果表明这种抑制活性可能受Notch调节。最后,我们认为Wingless信号传导由两个步骤组成,一个是下调调节dTcf活性的不依赖Su(H)的Notch活性,另一个是调节犰狳活性及其与dTcf相互作用的经典Wingless信号事件。