Loss of , an Arthrogryposis Multiplex Congenita Associated Gene, Promotes Osteoclastogenesis in Mice.

encodes a -type zinc finger protein, mutations of which lead to a spectrum of diseases known as associated rare disorders (ZARD). In addition to neurological phenotypes, the most typical symptoms of ZARD are multiple joint contractures of varying degrees, accompanied by abnormal development of muscles and bones, and osteoporosis in some cases. The pathogenic mechanisms of such bone related phenotypes, however, remain unclear.

RNF220 mediates K63-linked polyubiquitination of STAT1 and promotes host defense.

STAT1 is a master regulator that orchestrates type 1 and 2 interferon (IFN)-induced IFN-stimulated gene (ISG) expression. The mechanisms by which STAT1 is phosphorylated and activated upon IFN signaling remain elusive. Our work demonstrated that ubiquitination of STAT1 mediated by the E3 ligase RNF220 contributed significantly to STAT1 activation and innate immune responses.

Loss of ZC4H2 and RNF220 Inhibits Neural Stem Cell Proliferation and Promotes Neuronal Differentiation.

The ubiquitin E3 ligase RNF220 and its co-factor ZC4H2 are required for multiple neural developmental processes through different targets, including spinal cord patterning and the development of the cerebellum and the locus coeruleus. Here, we explored the effects of loss of ZC4H2 and RNF220 on the proliferation and differentiation of neural stem cells (NSCs) derived from mouse embryonic cortex. We showed that loss of either ZC4H2 or RNF220 inhibits the proliferation and promotes the differentiation abilities of NSCs in vitro.

EphA7 is required for otic epithelial homeostasis by modulating Claudin6 in Xenopus.

Receptor tyrosine kinase EphA7 is specifically expressed in otic region in Xenopus early development. However, its role in otocyst development remains unknown. Knockdown of EphA7 by a specific morpholino oligonucleotide (MO) reduced the size of the otocyst and triggered otic epithelial cell extrusion.

Fine-Tuning of Shh/Gli Signaling Gradient by Non-proteolytic Ubiquitination during Neural Patterning.

Sonic Hedgehog (Shh) signaling plays crucial roles in patterning the ventral neural tube, which is transformed into opposing gradients of repressor and activator forms of Glis. Here, we show that the fine-tuning of the shape of the Gli gradients through non-proteolytic ubiquitination-mediated nuclear exportation plays an important role in the control of local neural cell fate. Loss of RNF220, a ventral neural-specific ubiquitin E3 ligase, leads to ventral expansion of the intermediate V0 and dorsal expansion of the ventral V3 neurons, while reducing the V1, V2, and motor neurons between them.

EphA7 regulates claudin6 and pronephros development in Xenopus.

Eph/ephrin molecules are widely expressed during embryonic development, and function in a variety of developmental processes. Here we studied the roles of the Eph receptor EphA7 and its soluble form in Xenopus pronephros development. EphA7 is specifically expressed in pronephric tubules at tadpole stages and knockdown of EphA7 by a translation blocking morpholino led to defects in tubule cell differentiation and morphogenesis.

ZC4H2 stabilizes Smads to enhance BMP signalling, which is involved in neural development in .

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance, differentiation and embryonic development. Intracellularly, BMP signalling is mediated by Smad proteins, which are regulated post-transcriptionally through reversible phosphorylation and ubiquitination. ZC4H2 is a small nuclear protein associated with intellectual disability and neural development in humans.

Dual roles of Akirin2 protein during neural development.

To ensure correct spatial and temporal patterning, embryos must maintain pluripotent cell populations and control when cells undergo commitment. The newly identified nucleoprotein Akirin has been shown to modulate the innate immune response through epigenetic regulation and to play important roles in other physiological processes, but its role in neural development remains unknown. Here we show that Akirin2 is required for neural development in and that knockdown of Akirin2 expands the expression of the neural progenitor marker Sox2 and inhibits expression of the differentiated neuronal marker N-tubulin.

Trip12 is an E3 ubiquitin ligase for USP7/HAUSP involved in the DNA damage response.

The deubiquitinating enzyme, USP7/HAUSP (herpesvirus-associated ubiquitin-specific protease), is a key regulator of the tumor suppressor p53 and plays a major role in regulating genome stability. Here, we report that the protein stability of USP7 is regulated by the ubiquitin-proteasome pathway. We identified the thyroid hormone receptor interactor 12 (Trip12) as a ubiquitin E3 ligase for USP7.

EphA7 modulates apical constriction of hindbrain neuroepithelium during neurulation in Xenopus.

Eph receptor tyrosine kinases (RTKs) and their ephrin ligands play multiple roles in the developing nervous system, including cell segregation, axon guidance and synaptic plasticity. Here we report the expression and function of EphA7 in Xenopus hindbrain development. EphA7 is specifically expressed in the hindbrain throughout neurulation in Xenopus embryos.

Elongator Protein 3 (Elp3) stabilizes Snail1 and regulates neural crest migration in Xenopus.

Elongator protein 3 (Elp3) is the enzymatic unit of the elongator protein complex, a histone acetyltransferase complex involved in transcriptional elongation. It has long been shown to play an important role in cell migration; however, the underlying mechanism is unknown. Here, we showed that Elp3 is expressed in pre-migratory and migrating neural crest cells in Xenopus embryos, and knockdown of Elp3 inhibited neural crest cell migration.

A Group of ent-Kaurane Diterpenoids Inhibit Hedgehog Signaling and Induce Cilia Elongation.

The Hedgehog (Hh) signaling pathway plays important roles in the tumorigenesis of multiple cancers and is a key target for drug discovery. In a screen of natural products extracted from Chinese herbs, we identified eight ent-Kaurane diterpenoids and two triterpene dilactones as novel Hh pathway antagonists. Epistatic analyses suggest that these compounds likely act at the level or downstream of Smoothened (Smo) and upstream of Suppressor of Fused (Sufu).

Xenopus Claudin-6 is required for embryonic pronephros morphogenesis and terminal differentiation.

Claudins are tetratransmembrane tight junction proteins and play important roles in regulating paracellular permeability of different nephron segments of the kidney. However, the roles of claudins in kidney development remain largely unknown. Here we studied the expression and functions of claudin-6 in Xenopus pronephros development.

Xenopus Nkx6.3 is a neural plate border specifier required for neural crest development.

In vertebrates, the neural plate border (NPB) is established by a group of transcription factors including Dlx3, Msx1 and Zic1. The crosstalk between these NPB specifiers governs the separation of the NPB region into placode and neural crest (NC) territories and also their further differentiation. Understanding the mechanisms of NPB formation and NC development is critical for our knowledge of related human diseases.

The ubiquitin ligase RNF220 enhances canonical Wnt signaling through USP7-mediated deubiquitination of β-catenin.

Wnt/β-catenin signaling plays critical roles in embryonic development and disease. Here, we identify RNF220, a RING domain E3 ubiquitin ligase, as a new regulator of β-catenin. RNF220 physically interacts with β-catenin, but instead of promoting its ubiquitination and proteasomal degradation, it stabilizes β-catenin and promotes canonical Wnt signaling.

Dynamic expression of the LAP family of genes during early development of Xenopus tropicalis.

The leucine-rich repeats and PDZ (LAP) family of genes are crucial for the maintenance of cell polarity as well as for epithelial homeostasis and tumor suppression in both vertebrates and invertebrates. Four members of this gene family are known: densin, erbin, scribble and lano. Here, we identified the four members of the LAP gene family in Xenopus tropicalis and studied their expression patterns during embryonic development.

Dopamine D1 receptors are responsible for stress-induced emotional memory deficit in mice.

It is established that stress impairs spatial learning and memory via the hypothalamus-pituitary-adrenal axis response. Dopamine D1 receptors were also shown to be responsible for a stress-induced deficit of working memory. However, whether stress affects the subsequent emotional learning and memory is not elucidated yet.

Xenopus Dbx2 is involved in primary neurogenesis and early neural plate patterning.

The evolutionarily conserved Dbx homeodomain-containing proteins play important roles in the development of vertebrate central nervous system. In mouse, Dbx and Nkx6 have been suggested to be cross-repressive partners involved in the patterning of ventral neural tube. Here, we have isolated Xenopus Dbx2 and studied its developmental expression and function during neural development.

Xenopus RCOR2 (REST corepressor 2) interacts with ZMYND8, which is involved in neural differentiation.

Regulation of neuronal gene expression is critical to nervous system development. REST (RE1-silencing transcription factor) regulates neuronal gene expression through interacting with a group of corepressor proteins including REST corepressors (RCOR). Here we show that Xenopus RCOR2 is predominantly expressed in the developing nervous system.

RNF220, an E3 ubiquitin ligase that targets Sin3B for ubiquitination.

Modification of proteins by ubiquitination plays important roles in various cellular processes. During this process, the target specificity is determined by ubiquitin ligases. Here we identify RNF220 (RING finger protein 220) as a novel ubiquitin ligase for Sin3B.

Differential expression of the Brunol/CELF family genes during Xenopus laevis early development.

The BRUNOL/CELF family of RNA-binding proteins plays important roles in post-transcriptional regulation and has been implicated in several developmental processes. In this study, we describe the cloning and expression patterns of five Brunol genes in Xenopus laevis. Among them, only Brunol2 is maternally expressed and the zygotic expression of the other four Brunol genes starts at different developmental stages.

The effects of centrally administered fluorocitrate via inhibiting glial cells on working memory in rats.

Although prefrontal and hippocampal neurons are critical for spatial working memory, the function of glial cells in spatial working memory remains uncertain. In this study we investigated the function of glial cells in rats' working memory. The glial cells of rat brain were inhibited by intracerebroventricular (icv) injection of fluorocitrate (FC).

Aniracetam attenuates H2O2-induced deficiency of neuron viability, mitochondria potential and hippocampal long-term potentiation of mice in vitro.

Objective It is known that free radicals are involved in neurodegeneration and cognitive dysfunction, as seen in Alzheimer' s disease (AD) and aging. The present study examines the protective effects of aniracetam against H2O2-induced toxicity to neuron viability, mitochondria potential and hippocampal long-term potentiation (LTP). Methods Tetrazolium salt 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was used to detect neuronal viability.