Instituto de Medicina Molecular e Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Development. 2010 Nov;137(21):3625-32. doi: 10.1242/dev.054452. Epub 2010 Sep 28.
The importance of cilia in embryonic development and adult physiology is emphasized by human ciliopathies. Despite its relevance, molecular signalling pathways behind cilia formation are poorly understood. We show that Notch signalling is a key pathway for cilia length control. In deltaD zebrafish mutants, cilia length is reduced in Kupffer's vesicle and can be rescued by the ciliogenic factor foxj1a. Conversely, cilia length increases when Notch signalling is hyperactivated. Short cilia found in deltaD mutants reduce the fluid flow velocity inside Kupffer's vesicle, thus compromising the asymmetric expression of the flow sensor charon. Notch signalling brings together ciliary length control and fluid flow hydrodynamics with transcriptional activation of laterality genes. In addition, our deltaD mutant analysis discloses an uncoupling between gut and heart laterality.
人类纤毛病强调了纤毛在胚胎发育和成人生理学中的重要性。尽管如此，纤毛形成背后的分子信号通路仍知之甚少。我们发现 Notch 信号通路是控制纤毛长度的关键途径。在 deltaD 斑马鱼突变体中，Kupffer 囊泡中的纤毛长度减少，可以通过纤毛生成因子 foxj1a 来挽救。相反，当 Notch 信号通路过度激活时，纤毛长度会增加。在 deltaD 突变体中发现的短纤毛会降低 Kupffer 囊泡内的流体流速，从而损害流动传感器 charon 的不对称表达。Notch 信号通路将纤毛长度控制和流体流动动力学与偏侧性基因的转录激活联系在一起。此外，我们的 deltaD 突变体分析揭示了肠道和心脏偏侧性之间的分离。
