Background Kdm6b, a specific histone 3 lysine 27 (H3K27) demethylase, has been reported to be implicated in a variety of developmental processes including cell differentiation and cell fate determination and multiple organogenesis. Here, we regulated the transcript level of kdm6bb to study the potential role in controlling the hearing organ development of zebrafish. Methods A morpholino antisense oligonucleotide (MO) strategy was used to induce Kdm6b deficiency; immunohistochemical staining and in situ hybridization analysis were conducted to figure out the morphologic alterations and embryonic mechanisms. Results Kdm6bb is expressed in the primordium and neuromasts at the early stage of zebrafish embryogenesis, suggesting a potential function of Kdm6b in the development of mechanosensory organs. Knockdown of kdm6bb severely influences the cell migration and proliferation in posterior lateral line primordium, abates the number of neuromasts along the trunk, and mRNA-mediated rescue test can partially renew the neuromasts. Loss of kdm6bb might be related to aberrant expressions of chemokine genes encompassing cxcl12a and cxcr4b/cxcr7b in the migrating primordium. Moreover, inhibition of kdm6bb reduces the expression of genes in Fgf signaling pathway, while it increases the axin2 and lef1 expression level of Wnt/beta-catenin signaling during the migrating stage. Conclusions Collectively, our results revealed that Kdm6b plays an essential role in guiding the migration of primordium and in regulating the deposition of zebrafish neuromasts by mediating the gene expression of chemokines and Wnt and Fgf signaling pathway. Since histone methylation and demethylation are reversible, targeting Kdm6b may present as a novel therapeutic regimen for hearing disorders.
[1]Fudan Univ, ENT Inst, 83 Fenyang Rd, Shanghai 200031, Peoples R China.
[2]Fudan Univ, Dept Otorhinolaryngol, Eye & ENT Hosp, State Key Lab Med Neurobiol, 83 Fenyang Rd, Shanghai 200031, Peoples R China.
[3]Fudan Univ, MOE Frontiers Ctr Brain Sci, NHC Key Lab Hearing Med, 83 Fenyang Rd, Shanghai 200031, Peoples R China.
[4]Yijishan Hosp, Dept Otolaryngol Head & Neck Surg, Wannan Med Coll, 2 Zheshanwest Rd, Wuhu 241001, Anhui, Peoples R China.
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