He Yingzi, Tang Dongmei, Li Wenyan, Chai Renjie, Li Huawei
Otorhinolaryngology Department of Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200031, P.R. China.
Co-innovation Center of Neuroregeneration, Key Laboratory for Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu, 210096, P.R. China.
Sci Rep. 2016 Feb 1;6:16535. doi: 10.1038/srep16535.
Histone deacetylase 1 (HDAC1) has been reported to be important for multiple aspects of normal embryonic development, but little is known about its function in the development of mechanosensory organs. Here, we first confirmed that HDAC1 is expressed in the developing otic vesicles of zebrafish by whole-mount in situ hybridization. Knockdown of HDAC1 using antisense morpholino oligonucleotides in zebrafish embryos induced smaller otic vesicles, abnormal otoliths, malformed or absent semicircular canals, and fewer sensory hair cells. HDAC1 loss of function also caused attenuated expression of a subset of key genes required for otic vesicle formation during development. Morpholino-mediated knockdown of HDAC1 resulted in decreased expression of members of the Fgf family in the otic vesicles, suggesting that HDAC1 is involved in the development of the inner ear through regulation of Fgf signaling pathways. Taken together, our results indicate that HDAC1 plays an important role in otic vesicle formation.
据报道,组蛋白去乙酰化酶1(HDAC1)在正常胚胎发育的多个方面都很重要,但对其在机械感觉器官发育中的功能却知之甚少。在这里,我们首先通过整体原位杂交证实HDAC1在斑马鱼发育中的耳囊中表达。在斑马鱼胚胎中使用反义吗啉代寡核苷酸敲低HDAC1会导致耳囊变小、耳石异常、半规管畸形或缺失以及感觉毛细胞减少。HDAC1功能丧失还导致发育过程中耳囊形成所需的一组关键基因的表达减弱。吗啉代介导的HDAC1敲低导致耳囊中Fgf家族成员的表达降低,这表明HDAC1通过调节Fgf信号通路参与内耳的发育。综上所述,我们的结果表明HDAC1在耳囊形成中起重要作用。