Physiological effects of KDM5C on neural crest migration and eye formation during vertebrate development

Abstract

BackgroundLysine-specific histone demethylase 5C (KDM5C) belongs to the jumonji family of demethylases and is specific for the di- and tri-demethylation of lysine 4 residues on histone 3 (H3K4 me2/3). KDM5C is expressed in the brain and skeletal muscles of humans and is associated with various biologically significant processes. KDM5C is known to be associated with X-linked mental retardation and is also involved in the development of cancer. However, the developmental significance of KDM5C has not been explored yet. In the present study, we investigated the physiological roles of KDM5C during Xenopus laevis embryonic development.ResultsLoss-of-function analysis using kdm5c antisense morpholino oligonucleotides indicated that kdm5c knockdown led to small-sized heads, reduced cartilage size, and malformed eyes (i.e., small-sized and deformed eyes). Molecular analyses of KDM5C functional roles using whole-mount in situ hybridization, β-galactosidase staining, and reverse transcription-polymerase chain reaction revealed that loss of kdm5c resulted in reduced expression levels of neural crest specifiers and genes involved in eye development. Furthermore, transcriptome analysis indicated the significance of KDM5C in morphogenesis and organogenesis.ConclusionOur findings indicated that KDM5C is associated with embryonic development and provided additional information regarding the complex and dynamic gene network that regulates neural crest formation and eye development. This study emphasizes the functional significance of KDM5C in Xenopus embryogenesis; however, further analysis is needed to explore the interactions of KDM5C with specific developmental genes.Electronic supplementary materialThe online version of this article (10.1186/s13072-018-0241-x) contains supplementary material, which is available to authorized users.

Xenopus gpx3 Mediates Posterior Development by Regulating Cell Death during Embryogenesis

“…Xenopus embryos were fixed for 24 h in MEMFA at 4 °C and bleached (3% H 2 O 2 , 5% formamide, and 5xsaline sodium citrate (SSC)) after washing with phosphate buffer saline (PBS). The embryos were processed for TUNEL and PH3 staining, as described previously [ 28 ].…”

Epigenetic regulation of retinal development

“…In Xenopus , the lysine-specific histone demethylase 5C (Kdm5c) is also expressed in the embryonic eye and knockdown of Kdm5c results in smaller and deformed eyes, perturbed retinal lamination and abnormal RPE formation [ 73 ]. Knockout of Jmjd6 ( Ptdsr ) in mouse results in severe disruption in eye formation, with defects ranging from impaired retinal neuron differentiation to complete unilateral or bilateral anophthalmia [ 74 ].…”

X Inactivation and Escape: Epigenetic and Structural Features

“…For example, loss of function mutations in the escape gene, IQSEC2 , contribute to the manifestation of phenotypes that include moderate to severe intellectual disability (Shoubridge et al, 2019). Another example is KDM5C , an escape gene that encodes a histone demethylase and regulates neuronal development and function (Iwase et al, 2016; Scandaglia et al, 2017; Kim et al, 2018). Mutations in KDM5C cause intellectual disability in males and females, illustrating the dosage sensitivity of this gene (Brookes et al, 2015).…”