Polycomb group (PcG) proteins regulate the epigenetic status of transcription regulatory states during development. Progression from pluripotency to differentiation requires the sequential activation and repression of different PcG target genes, however, the relationship between early patterning signals, PcG expression, and the development of the central nervous system is still unclear. Using various models of neuronal differentiation, we provide evidence that CBX2 is a negative regulator of neuronal differentiation. Knock-down of CBX2 expression promotes neurite development, while overexpression of CBX2 inhibits neurite development. Further, we found that CBX2 is a direct target gene of miR-124. During neuronal differentiation, CBX2 was decreased while miR-124 was increased. Mechanistically, CBX2 directly interacts with the promoter region of several neuro-associated genes and regulates their expression. We found that the neuron-specific GAP-43 gene could contribute to the stimulating effect on neurite development associated with inhibition of CBX2.
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http://dx.doi.org/10.3389/fnmol.2018.00046 | DOI Listing |
Genes Cells
January 2025
Department of Genetic Biochemistry, The National Institutes of Biomedical Innovation, Health and Nutrition, Shinjuku-ku, Tokyo, Japan.
Catalytic subunit of DNA polymerase ζ (REV3), involved in translesion-replication is evolutionarily conserved from yeast and plants to higher eukaryotes. However, a large intermediate domain is inserted in REV3 of humans and mice. The domain has "DUF4683" region, which is significantly similar to human neurite extension and migration factor (NEXMIF).
View Article and Find Full Text PDFBMC Bioinformatics
January 2025
Centre for Quantitative Medicine, Duke-NUS Medical School, National University of Singapore, Singapore, Singapore.
Background: With the advance of next-generation sequencing, various gene-based rare variant association tests have been developed, particularly for binary and continuous phenotypes. In contrast, fewer methods are available for traits not following binomial or normal distributions. To address this, we previously proposed a set of burden- and kernel-based rare variant tests for count data following zero-inflated Poisson (ZIP) distributions, referred to as ZIP-b and ZIP-k tests.
View Article and Find Full Text PDFAdv Healthc Mater
January 2025
INL - International Iberian Nanotechnology Laboratory, Ultrafast Bio- and Nanophotonics group, Av. Mestre José Veiga s/n, Braga, 4715-330, Portugal.
Toward the aim of reducing animal testing, innovative in vitro models are required. Here, this study proposes a novel smart polymeric microscaffold to establish an advanced 3D model of dopaminergic neurons. These scaffolds are fabricated with Ormocomp via Two-Photon Polymerization.
View Article and Find Full Text PDFSci Rep
January 2025
Centro de Investigación en Medicina Traslacional "Severo R. Amuchástegui" (CIMETSA), Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Naciones Unidas 420, Barrio Parque Vélez Sarsfield, X5016KEJ, Córdoba, Argentina.
Extracellular vesicles (EVs) play a critical role in the development of neural cells in the central nervous system (CNS). Human neural rosettes (hNRs) are radial cell structures that assemble from induced pluripotent stem cells (hiPSCs) and recapitulate some stages of neural tube morphogenesis. Here we show that hiPSCs and hNRs secrete EVs (hiPSC-EVs and hNR-EVs) with distinctive protein cargoes.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
College of Veterinary Medicine, Konkuk University, 120, Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea. Electronic address:
Rett syndrome (RTT) is a neurological disorder caused by a mutation in the X-linked methyl-CpG binding protein 2 (MECP2), leading to cognitive and motor skill regression. Therapeutic strategies aimed at increasing brain-derived neurotrophic factor (BDNF) levels have been reported; however, BDNF treatment has limitations, including the inability to penetrate the blood-brain barrier, a short half-life, and potential for adverse effects when administered via intrathecal injection, necessitating novel therapeutic approaches. In this study, we focused on the adenosine A receptor (AR), which modulates BDNF and its downstream pathways, and investigated the therapeutic potential of CGS21680, an AR agonist, through in vitro and in vivo studies using R106W RTT model.
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