A body of evidence points to the matricial CCN proteins as key regulators of organogenesis. NOV/CCN3, a founder CCN member, is expressed in the developing central nervous system but its functions during neural development have not been studied yet. Here we describe the pattern of NOV expression during rat cerebellar postnatal development and show that NOV expression increases during the second postnatal week, a critical period for the maturation of granule neuron precursors (GNP). NOV transcripts are specifically produced by Purkinje neurons and NOV protein localises extracellularly in the molecular layer and the inner part of the external granule layer, at a key position to control GNP proliferation and migration. In vitro, NOV reduces Sonic Hedgehog-induced GNP proliferation through beta3 integrins and stimulation of GSK3-beta activity whereas NOV stimulates GNP migration through distinct RGD-dependent integrins. These findings identify a new paracrine role of NOV in the development of cerebellar granule neurons.
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http://dx.doi.org/10.1016/j.mcn.2009.02.011 | DOI Listing |
Elife
January 2025
Department of Neurobiology, Harvard Medical School, Boston, United States.
Unipolar brush cells (UBCs) are excitatory interneurons in the cerebellar cortex that receive mossy fiber (MF) inputs and excite granule cells. The UBC population responds to brief burst activation of MFs with a continuum of temporal transformations, but it is not known how UBCs transform the diverse range of MF input patterns that occur in vivo. Here, we use cell-attached recordings from UBCs in acute cerebellar slices to examine responses to MF firing patterns that are based on in vivo recordings.
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January 2025
Human Anatomy & Embryology Department, Faculty of Medicine, Zagazig University, Egypt.
Toxic-induced cerebellar syndrome (TOICS) poses substantial neurological challenges, given its diverse causes and complex manifestations. Gold nanoparticles (AuNPs) have gained significant attention owing to enhanced biocompatibility for therapeutic interventions. We aimed to investigate the impacts of AuNPs on cerebellar cytomolecular, immunohistochemical and ultrastructural alterations in the context of phenytoin-experimentally induced TOICS.
View Article and Find Full Text PDFNat Commun
January 2025
Neuronal Cell Biology Division, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38104, USA.
Exiting a germinal zone (GZ) initiates a cascade of events that promote neuronal maturation and circuit assembly. Developing neurons and their progenitors must interpret various niche signals-such as morphogens, guidance molecules, extracellular matrix components, and adhesive cues-to navigate this region. How differentiating neurons in mouse brains integrate and adapt to multiple cell-extrinsic niche cues with their cell-intrinsic machinery in exiting a GZ is unknown.
View Article and Find Full Text PDFCommun Biol
December 2024
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Brain-derived neurotrophic factor (BDNF) plays important roles in brain development and neural function. Constitutive knockout of the splicing regulator RBM4 reduces BDNF expression in the developing brain and causes cerebellar hypoplasia, an autism-like feature. Here, we show that Rbm4 knockout induced intron 6 retention of Hsf1, leading to downregulation of HSF1 protein and its downstream target BDNF.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Cellular and Molecular Neurobiology, Technische Universität Braunschweig, 38106, Braunschweig, Germany.
The cerebellum is a highly conserved brain compartment of vertebrates. Genetic diseases of the human cerebellum often lead to degeneration of the principal neuron, the Purkinje cell, resulting in locomotive deficits and socio-emotional impairments. Due to its relatively simple but highly conserved neuroanatomy and circuitry, these human diseases can be modeled well in vertebrates amenable for genetic manipulation.
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