Coordination of neuronal differentiation with expansion of the neuroepithelial/neural progenitor cell (NEPC/NPC) pool is essential in early brain development. Our in vitro and in vivo studies identify independent and opposing roles for two neural-specific and differentially expressed non-coding RNAs derived from the same locus: the evolutionarily conserved lncRNA Rncr3 and the embedded microRNA miR124a-1. Rncr3 regulates NEPC/NPC proliferation and controls the biogenesis of miR124a, which determines neuronal differentiation. Rncr3 conserved exons 2/3 are cytosine methylated and bound by methyl-CpG binding protein MeCP2, which restricts expression of miR124a embedded in exon 4 to prevent premature neuronal differentiation, and to orchestrate proper brain growth. MeCP2 directly binds cytosine-methylated Rncr3 through previously unrecognized lysine residues and suppresses miR124a processing by recruiting PTBP1 to block access of DROSHA-DGCR8. Thus, miRNA processing is controlled by lncRNA mC methylation along with the defined mC epitranscriptomic RNA reader protein MeCP2 to coordinate brain development.
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http://dx.doi.org/10.1038/s41467-024-49368-w | DOI Listing |
Dev Growth Differ
January 2025
Division of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.
The neural tube, the embryonic precursor to the vertebrate central nervous system, comprises distinct progenitor and neuronal domains, each with specific proliferation programs. In this study, we identified TMEM196, a novel transmembrane protein that plays a crucial role in regulating cell proliferation in the floor plate in chick embryos. TMEM196 is expressed in the floor plate, and its overexpression leads to reduced cell proliferation without affecting the pattern formation of the neural tube.
View Article and Find Full Text PDFNat Neurosci
January 2025
School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan.
Microglia-resident immune cells in the central nervous system-undergo morphological and functional changes in response to signals from the local environment and mature into various homeostatic states. However, niche signals underlying microglial differentiation and maturation remain unknown. Here, we show that neuronal micronuclei (MN) transfer to microglia, which is followed by changing microglial characteristics during the postnatal period.
View Article and Find Full Text PDFColloids Surf B Biointerfaces
January 2025
State Key Laboratory of Precision Manufacturing for Extreme Service Performance, College of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China; Jiangxi Province Key Laboratory of Additive Manufacturing of Implantable Medical Device, Jiangxi University of Science and Technology, Nanchang 330013, China. Electronic address:
Electrical stimulation displayed tremendous potential in promoting nerve regeneration. However, the current electrical stimulation therapy required complex traversing wires and external power sources, which significantly limited its practical application. Herein, a self-powered nerve scaffold based on primary battery principle was gradient printed by laser additive manufacturing technique.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China.
Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder characterized by a range of clinical manifestations with no effective treatment strategy to date. Here, transplantation of GABAergic precursor cells from the medial ganglionic eminence (MGE) is demonstrated to significantly improve cognitive performance in Fmr1 knockout (KO) mice. Within the hippocampus of Fmr1-KO mice, MGE-derived cells from wild-type donor mice survive, migrate, differentiate into functionally mature interneurons, and form inhibitory synaptic connections with host pyramidal neurons.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Biological Structure, University of Washington, Seattle, WA 98125.
Retinal diseases often lead to degeneration of specific retinal cell types with currently limited therapeutic options to replace the lost neurons. Previous studies have reported that overexpression of or combinations of proneural factors in Müller glia (MG) induce regeneration of functional neurons in the adult mouse retina. Recently, we applied the same strategy in dissociated cultures of fetal human MG and although we stimulated neurogenesis from MG, our effect in 2D cultures was modest and our analysis of newborn neurons was limited.
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