Takke C, Dornseifer P, v Weizsäcker E, Campos-Ortega J A
Institut für Entwicklungsbiologie, Universität zu Köln, Germany.
Development. 1999 May;126(9):1811-21. doi: 10.1242/dev.126.9.1811.
her4 encodes a zebrafish bHLH protein of the hairy-E(spl) family. The gene is transcribed in a complex pattern in the developing nervous system and in the hypoblast. During early neurogenesis, her4 expression domains include the regions of the neural plate from which primary neurons arise, suggesting that the gene is involved in directing their development. Indeed, misexpression of specific her4 variants leads to a reduction in the number of primary neurons formed. The amino-terminal region of her4, including the basic domain, and the region between the putative helix IV and the carboxy-terminal tetrapeptide wrpw are essential for this effect, since her4 variants lacking either of these regions are non-functional. However, the carboxy-terminal wrpw itself is dispensable. We have examined the interrelationships between deltaD, deltaA, notch1, her4 and neurogenin1 by means of RNA injections. her4 is involved in a regulatory feedback loop which modulates the activity of the proneural gene neurogenin, and as a consequence, of deltaA and deltaD. Activation of notch1 leads to strong activation of her4, to suppression of neurogenin transcription and, ultimately, to a reduction in the number of primary neurons. These results suggest that her4 acts as a target of notch-mediated signals that regulate primary neurogenesis.
her4编码一种属于hairy-E(spl)家族的斑马鱼bHLH蛋白。该基因在发育中的神经系统和下胚层中以复杂的模式转录。在早期神经发生过程中，her4的表达区域包括初级神经元产生的神经板区域，这表明该基因参与指导它们的发育。事实上，特定her4变体的错误表达会导致形成的初级神经元数量减少。her4的氨基末端区域，包括碱性结构域，以及假定的螺旋IV和羧基末端四肽wrpw之间的区域对这种效应至关重要，因为缺少这些区域之一的her4变体是无功能的。然而，羧基末端的wrpw本身是可有可无的。我们通过RNA注射研究了deltaD、deltaA、notch1、her4和神经生成素1之间的相互关系。her4参与一个调节反馈环，该反馈环调节神经原性基因神经生成素的活性，进而调节deltaA和deltaD的活性。notch1的激活导致her4的强烈激活，神经生成素转录的抑制，并最终导致初级神经元数量的减少。这些结果表明，her4作为notch介导信号调节初级神经发生的靶点发挥作用。
