He Yingzi, Lu Xiaoling, Qian Fuping, Liu Dong, Chai Renjie, Li Huawei
ENT Institute and Otorhinolaryngology Department of Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan UniversityShanghai, China.
Key Laboratory of Hearing Medicine of NHFPCShanghai, China.
Front Mol Neurosci. 2017 Aug 2;10:241. doi: 10.3389/fnmol.2017.00241. eCollection 2017.
Insulinoma-associated 1 (Insm1), a zinc-finger transcription factor, is widely expressed in the developing nervous system and plays important roles in cell cycle progression and cell fate specification. However, the functions of Insm1 in the embryonic development of the sensory system and its underlying molecular mechanisms remain largely unexplored. Here, through whole-mount hybridization, we found that the zebrafish gene was expressed in the posterior lateral line (pLL) system, including both the migrating pLL primordium and the deposited neuromast cells. In order to decipher the specific roles of in zebrafish pLL development, we inhibited expression by using a morpholino knockdown strategy. The morphants exhibited primordium migration defects that resulted in reduced numbers of neuromasts. The inactivation of reduced the numbers of hair cells in neuromasts, and this defect could be a secondary consequence of disrupting rosette formation in the pLL primordium. Additionally, we showed that knockdown decreased the proliferation of pLL primordium cells, which likely contributed to these pLL defects. Furthermore, we showed that loss of resulted in elevated Wnt/β-catenin signaling and downregulation of Fgf target genes in the primordium. knockdown also perturbed the expression patterns of chemokine signaling genes. Taken together, this study reveals a pivotal role for in regulating pLL development during zebrafish embryogenesis.
胰岛素瘤相关蛋白1(Insm1)是一种锌指转录因子,在发育中的神经系统中广泛表达,在细胞周期进程和细胞命运决定中发挥重要作用。然而,Insm1在感觉系统胚胎发育中的功能及其潜在分子机制在很大程度上仍未被探索。在此,通过全胚胎原位杂交,我们发现斑马鱼基因在后部侧线(pLL)系统中表达,包括迁移的pLL原基和沉积的神经丘细胞。为了解析Insm1在斑马鱼pLL发育中的具体作用,我们采用吗啉代敲低策略抑制其表达。Insm1敲低的胚胎表现出原基迁移缺陷,导致神经丘数量减少。Insm1失活减少了神经丘中毛细胞的数量,而这种缺陷可能是破坏pLL原基中玫瑰花结形成的继发后果。此外,我们发现敲低Insm1会降低pLL原基细胞的增殖,这可能导致了这些pLL缺陷。此外,我们还表明,Insm1缺失导致原基中Wnt/β-连环蛋白信号通路升高以及Fgf靶基因下调。敲低Insm1还扰乱了趋化因子信号基因的表达模式。综上所述,本研究揭示了Insm1在斑马鱼胚胎发育过程中调节pLL发育的关键作用。