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Conventionally, neuronal development is regarded to follow a stereotypic sequence of neurogenesis, migration, and differentiation. We demonstrate that this notion is not a general principle of neuronal development by documenting the timing of mitosis in relation to multiple differentiation events for bipolar cells (BCs) in the zebrafish retina using imaging. We found that BC progenitors undergo terminal neurogenic divisions while in markedly disparate stages of neuronal differentiation. Remarkably, the differentiation state of individual BC progenitors at mitosis is not arbitrary but matches the differentiation state of post-mitotic BCs in their surround. By experimentally shifting the relative timing of progenitor division and differentiation, we provide evidence that neurogenesis and differentiation can occur independently of each other. We propose that the uncoupling of neurogenesis and differentiation could provide neurogenic programs with flexibility, while allowing for synchronous neuronal development within a continuously expanding cell pool.
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http://dx.doi.org/10.15252/embj.201694230 | DOI Listing |
Alcohol Clin Exp Res (Hoboken)
September 2025
Department of Neuroscience and Experimental Therapeutics, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Background: Prenatal alcohol exposure (PAE) causes fetal alcohol spectrum disorder (FASD) and is associated with various cognitive and sensory impairments, including olfactory dysfunction. While both genetic and environmental factors contribute to olfactory dysfunction, PAE is considered a significant factor affecting brain development, including the olfactory system. In this study, we investigated the impact of PAE on the developing olfactory bulb (OB), specifically focusing on OB RGCs-radial glial cells that give rise to OB projection neurons.
View Article and Find Full Text PDFDev Biol
September 2025
School of Biological and Chemical Sciences, University of Galway, Biomedical Sciences Building, Newcastle Road, Galway H91 W2TY, Ireland. Electronic address:
The transcription factor Six1 and its co-activator Eya1 play central and varied roles during the development of sensory neurons derived from the cranial placodes in vertebrates. Previous studies suggested that these proteins promote both the maintenance of proliferative neuronal progenitors and neuronal differentiation. Context-specific interactions of Six1 and/or Eya1 with different cofactors are likely to contribute to the activation of distinct target genes during different stages of placodal neurogenesis.
View Article and Find Full Text PDFStem Cell Reports
September 2025
Neural Stem Cells and Neuroimaging Group, Department of Neurobiology, Hellenic Pasteur Institute, 11521 Athens, Greece. Electronic address:
In the adult brain, neural stem cells (NSCs) constitutively generate new neurons in specific neurogenic domains. Recent research has unveiled reactive neurogenesis, whereby brain injury triggers NSC activation, enhancing their differentiation potential and guiding progeny to injured areas. Our study provides evidence of alternative migration pathways for newborn neurons in the mouse subcortical forebrain, revealed by administration of a chemotherapeutic agent.
View Article and Find Full Text PDFStem Cell Reports
September 2025
Child Study Center, Yale University, New Haven, CT 06520, USA; Program in Neurodevelopment and Regeneration, Yale University, New Haven, CT 06520, USA; Department of Neuroscience, Yale University, New Haven, CT 06520, USA; Yale Stem Cell Center, Yale University, New Haven, CT 06520, USA. Electronic
A complex assortment of neuronal cells contributes to distinct functional circuits in the human brain. Such diversity is imposed upon pluripotent stem cells by a patterning process that begins much before the start of neurogenesis. Neural tube patterning relies on morphogens-diffusible signals that regulate transcription factor networks in progenitor cells, guiding spatial and temporal identity formation.
View Article and Find Full Text PDFStem Cell Reports
September 2025
Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy. Electronic address:
Human brain organoids, generated from pluripotent stem cells, recapitulate fundamental features of human brain development, including neuronal diversity, regional architecture, and functional network activity. Integrated multimodal and transcriptomic analyses reveal a molecular repertoire of ionotropic receptors supporting action potentials, synaptic transmission, and oscillatory dynamics resembling early brain activity. This review synthesizes current knowledge on the molecular and electrophysiological determinants of neuronal maturation and network computations, from synaptic integration to large-scale dynamics.
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