![]() 9, 10Įpigenetics is on the study of heritable and reversible changes in gene expression patterns rather than altering the intrinsic DNA sequence. 6 In addition to the genetic mechanism, there are also epigenetic mechanisms in the development of inner ear. 8 The formation of inner ear is a complex process, involving multiple factors and multistep actions. 6, 7 The utricular macula has vestibular (balance) function, while the saccular macula has a primarily auditory (hearing) function. 5, 6The inner ear of zebrafish is composed of three pairs of semicircular canals (anterior, posterior and lateral) and two pairs of otolith organs named utricle and saccule. 4 The mature neuromasts are composed of hair cells (HCs) and surrounding supporting cells, which are structurally and functionally similar with mammalian inner ear. 3 The PLL primordium is a cluster of 100–150 cells that have the ability to migrate caudally to the end of the embryo, periodically deposit neuromasts at regular intervals, and finally form five or six truncal neuromasts and two or three terminal neuromasts. 1, 2 The lateral line system is the sensory organ of zebrafish that detects water movements and sound, which is composed of the anterior lateral line in the head region and the posterior lateral line (PLL) behind the inner ear. The zebrafish model has been increasingly applied in understanding the molecular genetic principle of inner ear dysplasia and related diseases. Thus, detecting the pivotal genes during auditory organogenesis is crucial to explore the potential strategy for hearing impairment. Hearing disorders, often related to inner ear agenesis or injury, are serious health issues that affect quality of life. Further ISH analysis confirmed the findings by RNA‐seq and WGBS assay that cdkn1a and tp53 were both upregulated after knockdown of Dnmt1. ![]() The WGBS analysis demonstrated that the global methylation status was markedly downregulated, and cell cycle genes were among those most differently expressed between Dnmt1 morphants and the controls. The in situ staining of otic placode markers pax2/5 and fgf 3/8/10 was decreased when Dnmt1 downregulated. Additionally, Dnmt1 downregulation led to malformed otoliths and deformed semicircular canals, and hair cell differentiation in utricle and saccule was inhibited severely. The ISH data uncovered that Fgf signalling pathway was inhibited and the expression of chemokine members cxcr4b, cxcr7b and cxcl12a were interfered, while lef1 expression was increased after inhibiting Dnmt1. We found that downregulation of Dnmt1 induced decreased number of neuromasts and repressed cell proliferation of primordium in the developing posterior lateral line system of zebrafish. ![]()
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