Lysine demethylase 3a in craniofacial and neural development during Xenopus embryogenesis

Abstract

Epigenetic modifier lysine demethylase 3a (Kdm3a) specifically demethylates mono-and di-methylated ninth lysine of histone 3 and belongs to the Jumonji domain-containing group of demethylases. Kdm3a serves roles during various biological and pathophysiological processes, including spermatogenesis and metabolism, determination of sex, androgen receptor-mediated transcription and embryonic carcinoma cell differentiation. In the present study, physiological functions of Kdm3a were evaluated during embryogenesis of Xenopus laevis. Spatiotemporal expression pattern indicated that kdm3a exhibited its expression from early embryonic stages until tadpole stage, however considerable increase of kdm3a expression was observed during the neurula stage of Xenopus development. Depleting kdm3a using kdm3a antisense morpholino oligonucleotides induced anomalies, including head deformities, small-sized eyes and abnormal pigmentation. Whole-mount in situ hybridization results demonstrated that kdm3a knockdown was associated with defects in neural crest migration. Further, quantitative polymerase chain reaction revealed abnormal expression of neural markers in kdm3a morphants. RNA sequencing of kdm3a morphants indicated that kdm3a was implicated in mesoderm formation, cell adhesion and metabolic processes of embryonic development. In conclusion, the results of the present study indicated that Kdm3a may serve a role in neural development during Xenopus embryogenesis and may be targeted for treatment of developmental disorders. Further investigation is required to elucidate the molecular mechanism underlying the regulation of neural development by Kdm3a.

Time to go: neural crest cell epithelial-to-mesenchymal transition

“…Interestingly, the loss of KDM5C has no effect on Sox9 expression, which may explain the absence of cranial cartilage deformities in KDM5C-deficient frogs. Also in X. laevis , KDM3A is expressed from early embryonic stages to tadpole stage, with a dramatic increase in expression during neurula stage ( Lee et al, 2019 ). Knockdown of KDM3A impairs NCC migration, which could be explained by changes in the expression of factors that regulate mesoderm formation, cell adhesion and metabolic processes ( Lee et al, 2019 ).…”

Knockout of KDM3A in MDA-MB-231 breast cancer cells inhibits tumor malignancy and promotes apoptosis

“…KDM3A, a critical member of the H3K9me2/1 demethylase family, exhibits diverse regulatory functions in association with target genes. Its involvement in the core regulatory mechanisms governing the proliferation and differentiation of neural stem cells, hematopoietic stem cells (Ikeda et al 2018 ), and embryonic stem cells underscores its significance in tumorigenesis (Lee et al 2019 ), development (Wang et al 2019 ) and metastasis (Li et al 2017 ). Suppression of KDM3A has been shown to inhibit cell proliferation (Qin et al 2017 ; Wilson et al 2017 ), while further depletion of KDM3A demonstrates inhibitory effects on cell proliferation, migration, and invasion (Ikeda et al 2018 ; Ramadoss et al 2017a ; Sun et al 2019 ).…”

The evolution of tribological properties of graphite and glass fiber reinforced novolac matrix hybrid composites

“…[3][4][5] Although the performance of friction composites has yielded different results in different applications, the results can be divided into certain groups. Asbestos, which was the most important component of commercially produced friction materials in the past, has begun to be replaced by new materials such as ceramic fibers, [6,7] organic fibers, [8,9] metal fibers, [10,11] and carbon fibers [12,13] as reinforcements. Selecting and designing a high-quality friction materials consisting of many components is a challenging task.…”