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

Background: Lysine-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. Results: Loss-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, -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. Conclusion: Our 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

Transcriptional analysis of the Differentiation of Dorsal Marginal Zone (DMZ)

The dorsal marginal zone (DMZ) is an important tissue region in Xenopus early gastrula stage because it contains Spermann-Mangold organizer. Also, it has precursors for all three germ layers in development: endoderm, mesoderm, and ectoderm. To identify gene related to the differentiation of DMZ, we analyzed the time course gene expression data of Xenopus laevis DMZ from stage 10 to stage 18. Surprisingly, the gene expression pattern was clearly divided into two groups as DMZ was developed. As we wanted to know differentiation onset related gene signaling, the group of genes with GO terms like cell differentiation, cell proliferation, and circadian regulation were further analyzed. Through this analysis, we found a transcription factor related to cell proliferation and differentiation in DMZ. Furthermore, activated or repressed genes were surveyed and supported by their expression pattern. We will also present the pathways putatively important in DMZ development

A temporally resolved transcriptome for developing ???Keller??? explants of the Xenopus laevis dorsal marginal zone

Background Explanted tissues from vertebrate embryos reliably develop in culture and have provided essential paradigms for understanding embryogenesis, from early embryological investigations of induction, to the extensive study of Xenopus animal caps, to the current studies of mammalian gastruloids. Cultured explants of the Xenopus dorsal marginal zone (???Keller??? explants) serve as a central paradigm for studies of convergent extension cell movements, yet we know little about the global patterns of gene expression in these explants. Results In an effort to more thoroughly develop this important model system, we provide here a time???resolved bulk transcriptome for developing Keller explants. Conclusions The dataset reported here provides a useful resource for those using Keller explants for studies of morphogenesis and provide genome???scale insights into the temporal patterns of gene expression in an important tissue when explanted and grown in culture

Adaptive cellular response of the substantia nigra dopaminergic neurons upon age-dependent iron accumulation

Progressive iron accumulation in the substantia nigra in the aged human brain is a major risk factor for Parkinson's disease and other neurodegenerative diseases. Heavy metals, such as iron, produce reactive oxygen species and consequently oxidative stress in cells. It is unclear, however, how neurons in the substantia nigra are protected against the age-related, excessive accumulation of iron. In this study, we examined the cellular response of the substantia nigra against age-related iron accumulation in rats of different ages. Magnetic resonance imaging confirmed the presence of iron in 6-month-old rats; in 15-month-old rats, iron accumulation significantly increased, particularly in the midbrain. Transcriptome analysis of the region, in which iron deposition was observed, revealed an increase in stress response genes in older animals. To identify the genes related to the cellular response to iron, independent of neurodevelopment, we exposed the neuroblastoma cell line SH-SY5Y to a similar quantity of iron and then analyzed their transcriptomic responses. Among various stress response pathways altered by iron overloading in the rat brain and SH-SY5Y cells, the genes associated with topologically incorrect protein responses were significantly upregulated. Knockdown of HERPUD1 and CLU in this pathway increased susceptibility to iron-induced cellular stress, thus demonstrating their roles in preventing iron overload-induced toxicity. The current study details the neuronal response to excessive iron accumulation, which is associated with age-related neurodegenerative diseases