XIPOU 2, a member of the class III POU domain family, is expressed initially in Spemann's organizer, and later, in discrete regions of the developing nervous system in Xenopus laevis. XIPOU 2 may act downstream from initial neural induction events, since it is activated by the neural inducer, noggin. To determine if XIPOU 2 participates in the early events of neurogenesis, synthetic mRNA was microinjected into specific blastomeres of the 32-cell stage embryo. Misexpression of XIPOU 2 in the epidermis causes a direct switch in cell fate from an epidermal to a neuronal phenotype. In the absence of mesoderm induction, XIPOU 2 has the ability to induce a neuronal phenotype in uncommitted ectoderm. These data demonstrate the potential of XIPOU 2 to act as a master regulator of neurogenesis.
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http://dx.doi.org/10.1242/dev.121.3.721 | DOI Listing |
Neuron
March 2025
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Solomon H. Snyder Department of Neuroscience and Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address:
The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the repeat expansion in C9ORF72. Dipeptide repeat (DPR) proteins translated from both sense and antisense repeats, especially arginine-rich DPRs (R-DPRs), contribute to neurodegeneration. Through CRISPR interference (CRISPRi) screening in human-derived neurons, we identified receptor-type tyrosine-protein phosphatase S (PTPσ) as a strong modifier of poly-GR-mediated toxicity.
View Article and Find Full Text PDFBrain
March 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
Patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, often present with severe psychiatric symptoms, yet the neuropathological mechanisms underlying their cognitive deficits remain insufficiently understood. In this study, we constructed an animal model using anti-NMDAR IgG purified from the serum of patients with anti-NMDAR encephalitis, and we used IgG obtained from healthy individuals as a control. Daily administration of anti-NMDAR IgG into the medial prefrontal cortex (mPFC) of mice for 7 days resulted in cognitive impairments resembling clinical symptoms, which spontaneously resolved 30 days after discontinuing the injections.
View Article and Find Full Text PDFJ Pain Res
March 2025
Department of Pain, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, People's Republic of China.
Background: Patients with neuropathic pain (NP), caused by injury or disease of the somatosensory nervous system, usually suffer from severe pain. Our previous studies revealed that electroacupuncture (EA) stimulation could effectively improve NP. However, the underlying mechanisms of EA have not been fully clarified.
View Article and Find Full Text PDFACS Chem Neurosci
March 2025
Department of Chemistry and Biochemistry, University of Denver, F.W. Olin Hall, 2190 E Iliff Ave, Denver, Colorado 80210, United States.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the leading cause of dementia, affecting nearly 55 million people across the world. One of the central pathological factors associated with AD is the aggregation of Aβ, a peptide product cleaved through pathological processes in AD. Under pathological conditions, Aβ aggregates into insoluble plaques in the brain and impairs the function of neurons, which contributes to the cognitive decline associated with AD.
View Article and Find Full Text PDFCommun Biol
March 2025
Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, CH-8032, Switzerland.
Methylmalonic aciduria (MMA) is an inborn error of metabolism resulting in loss of function of the enzyme methylmalonyl-CoA mutase (MMUT). Despite acute and persistent neurological symptoms, the pathogenesis of MMA in the central nervous system is poorly understood, which has contributed to a dearth of effective brain specific treatments. Here we utilised patient-derived induced pluripotent stem cells and in vitro differentiation to generate a human neuronal model of MMA.
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