Neural induction is a process where naive cells are converted into committed cells with neural characteristics, and it occurs at the earliest step during embryogenesis. Although the signaling molecules and chromatin remodeling for neural induction have been identified, the mutual relationships between these molecules are yet to be fully understood. By taking advantage of the neural differentiation system of mouse embryonic stem (ES) cells, we discovered that the BMP signal regulates the expression of several polycomb repressor complex (PRC) component genes. We particularly focused on Polyhomeotic Homolog 1 (Phc1) and established -knockout (-KO) ES cells. We found that -KO failed to acquire the neural fate, and the cells remained in pluripotent or primitive non-neural states. Chromatin accessibility analysis suggests that Phc1 is essential for chromatin packing. Aberrant upregulation of the BMP signal was confirmed in the homozygotic mutant embryos. Taken together, Phc1 is required for neural differentiation through epigenetic modification.
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http://dx.doi.org/10.1016/j.isci.2023.107887 | DOI Listing |
Development
January 2025
The Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
Tissue development relies on the coordinated differentiation of stem cells in dynamically changing environments. The formation of the vertebrate neural tube from stem cells in the caudal lateral epiblast (CLE) is a well characterized example. Despite an understanding of the signalling pathways involved, the gene regulatory mechanisms remain poorly defined.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, UAE; Zayed Center for Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, UAE; ASPIRE Precision Medicine Research Institute Abu Dhabi (PMRI-AD), United Arab Emirates University, Al Ain, UAE. Electronic address:
Neurodevelopmental disorders have complex origins that manifest early during embryonic growth and are associated with intricate gene regulation dynamics. A perturbed metabolic environment such as hyperglycemia or dyslipidemia, particularly due to maternal obesity, poses a threat to the optimal development of the embryonic central nervous system. Accumulating evidence suggests that these metabolic irregularities during pregnancy may alter neurogenesis pathways, thereby predisposing the developing fetus to neurodevelopmental disorders.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Division of Biotechnologies, Italian National Agency for Energy, New Technologies and Sustainable Economic Development (ENEA), 00123 Rome, Italy.
In the tissue regeneration field, stem cell transplantation represents a promising therapeutic strategy. To favor their implantation, proliferation and differentiation need to be controlled. Several studies have demonstrated that stem cell fate can be controlled by applying continuous electric field stimulation.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry & Molecular Biology, Medical Primate Research Center, Neuroscience Center, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
The development of the mammalian neocortex is precisely regulated by temporal gene expression, yet the temporal regulatory mechanisms of cortical neurogenesis, particularly how radial glial cells (RGCs) sequentially generate deep to superficial neurons, remain unclear. Here, the hnRNP family member Syncrip (hnRNP Q) is identified as a key modulator of superficial neuronal differentiation in neocortical neurogenesis. Syncrip knockout in RGCs disrupts differentiation and abnormal neuronal localization, ultimately resulting in superficial cortical layer defects as well as learning and memory impairments in mice.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Ophthalmology, University of California San Francisco, San Francisco, CA 94158, USA.
Neurons use cell-adhesion molecules (CAMs) to interact with other neurons and the extracellular environment: the combination of CAMs specifies migration patterns, neuronal morphologies, and synaptic connections across diverse neuron types. Yet little is known regarding the intracellular signaling cascade mediating the CAM recognitions at the cell surface across different neuron types. In this study, we investigated the neural developmental role of Afadin, a cytosolic adapter protein that connects multiple CAM families to intracellular F-actin.
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