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

Zhang, Longlong; Ye, Maosen; Zhu, Liang; Cha, Jingmei; Li, Chaocui; Yao, Yong-Gang; Mao, Bingyu

doi:10.3390/cells9071600

Cited by 12 publications

(7 citation statements)

References 33 publications

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“…At present, it is well known that both RNF220 and its co-factor ZC4H2 are required for multiple neural developmental processes, including spinal cord patterning, cerebellum embryogenesis and function, and activity of the locus coeruleus ( 26 ). A study by Ma et al using Zc4h2 knockdown mice models revealed peculiar alterations in the V2a and V2b hindbrain and spinal cord interneurons, potentially implicating such features in the neuronal (and thus neurodevelopmental) phenotypes associated with WWS ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report

et al. 2021

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Wieacker-Wolff syndrome (WWS) is an X-linked Arthrogryposis Multiplex Congenita (AMC) disorder associated with broad neurodevelopmental impairment. The genetic basis of WWS lies in hemizygous pathogenic variants in ZC4H2, encoding a C4H2 type zinc-finger nuclear factor abundantly expressed in the developing human brain. The main clinical features described in WWS families carrying ZC4H2 pathogenic variants encompass having a short stature, microcephaly, birth respiratory distress, arthrogryposis, hypotonia, distal muscle weakness, and broad neurodevelopmental delay. We hereby report a Sicilian family with a boy clinically diagnosed with WWS and genetically investigated with exome sequencing (ES), leading to the identification of a c.593G>A (p. R198Q) hemizygous pathogenic variant in the ZC4H2 gene. During the first year of life, the onset of central hypoadrenalism led to recurrent hypoglycemic events, which likely contributed to seizure susceptibility. Also, muscle biopsy studies confirmed a pathology of the muscle tissue and revealed peculiar abnormalities of the neuromuscular junction. In conclusion, we expand the phenotypic spectrum of the WWS-related neurodevelopmental disorders and discuss the role of ZC4H2 in the context of the potential neuroendocrinological and neuromuscular features associated with this condition.

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Section: Discussionmentioning

confidence: 99%

Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report

et al. 2021

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“…The different signal pathway regulation regulated the differentiation and proliferation of NSC. The differentiated signal pathway activity is relatively low or inhibited when proliferation is enhanced (53). In the present study, 1 µM BPA could promote human NSC proliferation and stemness.…”

Section: Discussionmentioning

confidence: 51%

Roles of ERRα and TGF‑β signaling in stemness enhancement induced by 1 µM bisphenol A exposure via human neural stem cells

Dong¹,

Ye²,

Tu³

et al. 2021

Exp Ther Med

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Bisphenol A (BPA) is a common industrial chemical widely used to produce various plastics and is known to impair neural stem cells (NSCs). However, the effects of low-dose BPA exposure on the stemness maintenance and differentiation fate of NSCs remain unclear in the infant brain. The present study demonstrated that 1 µM BPA promoted human NSC proliferation and stemness, without significantly increasing apoptosis. The Chip-seq experiments demonstrated that both the cell cycle and the TGF-β signaling pathway were accelerated after treatment with 1 µM BPA. Subsequently, estrogen-related receptor α (ERRα) gene knockout cell lines were constructed using CRISPR/Cas9. Further western blotting and chromatin immunoprecipitation-PCR experiments demonstrated that BPA maintained cell stemness by binding to an EERα receptor and activating the TGF-β1 signaling pathway, including the downstream factors Aurora kinases B and Id2. In conclusion, the stemness of NSCs could be maintained by BPA at 1 µM through the activation of the ERRα and TGF-β1 signaling pathways and could restrain the differentiation of NSCs into neurons. The present research further clarified the mechanism of BPA toxicity on NSCs from the novel perspective of ERRα and TGF-β1 signaling pathways regulated by BPA and provided insights into potential novel methods of prevention and therapy for neurogenic diseases.

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“…Unexpectedly, in an RNA-seq analysis, few overlapping differentially expressed genes were identified in the ZC4H2 −/− and RNF220 −/− NSCs, suggesting the potential non-RNF220-dependent roles of ZC4H2 in NSCs; however, this requires further analysis (Zhang et al, 2020).…”

Section: P Otential Role S Of Rnf22 0/zc4h2 In Neur Al S Tem Cell Smentioning

confidence: 90%

The many faces of the E3 ubiquitin ligase, RNF220, in neural development and beyond

Mao

2021

Dev Growth Differ

Self Cite

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Protein ubiquitination, an important posttranslational modification, is involved in almost all biological processes in eukaryotes (Zheng & Shabek, 2017). During embryonic development, protein ubiquitination plays a critical role in controlling signaling pathways that are essential for developmental patterning and determination of cell fate (Rape, 2017). Ubiquitination of target proteins is catalyzed by a three-step enzymatic cascade, including E1 ubiquitin-activating, E2 ubiquitin-conjugating, and E3 ubiquitin-ligating enzymes (Pickart, 2001). Ubiquitin has seven lysine (K) residues (K6, K11, K27, K29, K33, K48, and K63) that are involved in the formation polyubiquitin chains of different linkage types. Different linked polyubiquitin chains invoke various functional outcomes specific for each target protein. The most abundant polyubiquitin chains are K48-and K63linked chains, where the K48-linked chains function as a signal for

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

Cited by 12 publications

References 33 publications

Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report

Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report

Roles of ERRα and TGF‑β signaling in stemness enhancement induced by 1 µM bisphenol A exposure via human neural stem cells

The many faces of the E3 ubiquitin ligase, RNF220, in neural development and beyond

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