External granule layer

Sorting maturing neurons into distinct layers is critical for brain development, with disruptions leading to neurological disorders and pediatric cancers. Lamination coordinates where, when, and how cells interact, facilitating events that direct migrating neurons to their destined positions within emerging neural networks and control the wiring of connections in functional circuits. While the role of adhesion molecule expression and presentation in driving adhesive recognition during neuronal migration along glial fibers is recognized, the mechanisms by which the spatial arrangement of these molecules on the cell surface dictates adhesive specificity and translates contact-based external cues into intracellular responses like polarization and cytoskeletal organization remain largely unexplored...

Internal granular progenitors (IGPs) in the developing cerebellar cortex of ferrets differentiate towards neural and glial lineages. The present study tracked IGPs that proliferated in response to valproic acid (VPA) to determine their fate during cerebellar cortical histogenesis. Ferret kits were used to administer VPA (200 μg/g body weight) on postnatal days 6 and 7. EdU and BrdU were injected on postnatal days 5 and 7, respectively, to label the post-proliferative and proliferating cells when exposed to VPA...

OBJECTIVE: The cerebellum has a long, protracted developmental period; therefore, it is more sensitive to intrauterine and postnatal insults like nutritional deficiencies. Folate is an essential nutrient in fetal and postnatal brain development, and its supplementation during pregnancy is widely recommended. This study aimed to describe the effects of maternal folate intake on postnatal cerebellum development. METHODS: Twelve adult female Rattus norwegicus (6-8 weeks old) rats were randomly assigned to one of four groups and given one of four premixed diets: a standard diet (2 mg/kg), a folate-deficient (folate 0 mg/kg), folate-supplemented (8 mg/kg), or folate supra-supplemented (40 mg/kg)...

Modeling has proposed that the amount of neural tissue folding is set by the level of differential-expansion between tissue layers and that the wavelength is set by the thickness of the outer layer. Here we used inbred mouse strains with distinct amounts of cerebellar folding to investigate these predictions. We identified distinct critical periods where the folding amount diverges between the two strains. In this period, regional changes in the level of differential-expansion between the external granule layer (EGL) and underlying core correlate with the folding amount in each strain...

In this study, the filamentous bulking (FB) with moderate and excessive levels were demonstrated to induce anammox failure by inhibiting nitrogen (N) removal and biomass retention. The low external mass transfer resulted from high liquid-surface friction and low turbulence of filamentous surface was considered the "trigger" of anammox failure, which decreased flux of nitrogen flow toward granular surface and directly limited N-removal loading, which meanwhile exposed granules with N-scarcity environment and indirectly inhibited N-removal bio-activity...

BACKGROUND: Thyroid hormones, which produce critical changes in our bodies even when their physiological levels alter slightly, are crucial hormones that influence gene transcription. Neuronal plasticity, on the other hand, requires both the activation of local proteins as well as protein translation and transcription in response to external signals. To far, no study has examined metaplastic long-term potentiation and related gene expression levels in a hyperthyroid experimental model...

Wounds and the healing process are one of the main concerns of medical science today. A wound is any loss of integrity, or rupture of the layers of skin (epidermis, dermis, and hypodermis) or subcutaneous tissue caused by physical factors (surgical incision, trauma, pressure, and gunshot wounds) or chemical factors (acid burns). It is observed that soft tissue, muscle, or bone is involved in occurrences of wounds. Lesions and fractures of the skin surface necessitate medical attention, wherein dressings expedite the healing process by establishing a physical barrier between the wound and the external environment, thereby preventing further injury or infection...

INTRODUCTION: Brain connectivity requires correct axonal guidance to drive axons to their appropriate targets. This process is orchestrated by guidance cues that exert attraction or repulsion to developing axons. However, the intricacies of the cellular machinery responsible for the correct response of growth cones are just being unveiled. Netrin-1 is a bifunctional molecule involved in axon pathfinding and cell migration that induces repulsion during postnatal cerebellar development...

Glucocorticoids administered early in infancy can affect the architectonic organization of brain structures, particularly those with a postnatal development and resulting in long-term deficits of neuromotor function and cognition. The present study was undertaken to study the effects of daily corticosterone (CORT) injections at a pharmacological dose from postnatal days 8-15 on cerebellar and hippocampal development in mouse pups. Gene expression status for trophic factors involved in synaptic development and function as well as measures of layer thickness associated with cytochrome oxidase labelling were analyzed in the hippocampus, hypothalamus, and specific cerebellar lobules involved in motor control...

Modeling has proposed that the amount of neural tissue folding is set by the level of differential-expansion between tissue layers and that the wavelength is set by the thickness of the outer layer. Here we used inbred mouse strains with distinct amounts of cerebellar folding to investigate these predictions. We identified a critical period where the folding amount diverges between the strains. In this period, regional changes in the level of differential-expansion between the external granule layer (EGL) and underlying core correlate with the folding amount in each strain...

Over the past decade, survival rates for extremely low gestational age neonates (ELGANs; <28 weeks gestation) has markedly improved. Unfortunately, a significant proportion of ELGANs will suffer from neurodevelopmental dysfunction. Cerebellar hemorrhagic injury (CHI) has been increasingly recognized in the ELGANs population and may contribute to neurologic dysfunction; however, the underlying mechanisms are poorly understood. To address this gap in knowledge, we developed a novel model of early isolated posterior fossa subarachnoid hemorrhage (SAH) in neonatal mice and investigated both acute and long-term effects...

The difficulty of retrieving high-resolution, in vivo evidence of the proliferative and migratory processes occurring in neural germinal zones has limited our understanding of neurodevelopmental mechanisms. Here, we used a connectomic approach using a high-resolution, serial-sectioning scanning electron microscopy volume to investigate the laminar cytoarchitecture of the transient external granular layer (EGL) of the developing cerebellum, where granule cells coordinate a series of mitotic and migratory events...

UNLABELLED: The expression and processing of filaggrin, a filament-associated protein in the skin epidermis, is closely associated with keratinocyte cornification. The large precursor profilaggrin (Pro-FLG) is initially detected at the granular layer in keratohyalin granules, subsequently processed into 10 to 12 filaggrin monomers (mFLGs) for keratin assembly, and ultimately degraded into smaller peptides that behave as natural moisturizing factor (NMF) at the outermost epidermis. We previously reported that epimorphin (EPM) extruded upon external stimuli severely perturbs epidermal terminal differentiation...

Development of the cerebellum is characterized by rapid proliferation of cerebellar granule cell precursors (GCPs) induced by paracrine stimulation of Sonic hedgehog (Shh) signaling from Purkinje cells, in the external granular layer (EGL). Then, granule cell precursors differentiate and migrate into the inner granular layer (IGL) of the cerebellum to form a terminally differentiated cell compartment. Aberrant activation of Sonic hedgehog signaling leads to granule cell precursors hyperproliferation and the onset of Sonic hedgehog medulloblastoma (MB), the most common embryonal brain tumor...

To analyze the role of syndecan-3 (SDC3), a heparan sulfate proteoglycan, in cerebellum development, we examined the effect of SDC3 on the transition from cell cycle exit to the initial differentiation stage of cerebellar granule cell precursors (CGCPs). First, we examined SDC3 localization in the developing cerebellum. SDC3 was mainly localized to the inner external granule layer where the transition from the cell cycle exit to the initial differentiation of CGCPs occurs. To examine how SDC3 regulates the cell cycle exit of CGCPs, we performed SDC3-knockdown (SDC3-KD) and -overexpression (Myc-SDC3) assays using primary CGCPs...

OBJECTIVE: The aim: To examine morphological peculiarities of the skin granulation tissue from the laparotomy wound in patients with malignant neoplasms of the abdominal organs. PATIENTS AND METHODS: Materials and methods: 36 bodies of deceased people were examined after midline laparotomy performed for surgical treatment of diseases of the abdominal organs. The main group included 22 bodies of deceased people suffering from malignant neoplasms of the abdominal organs, mostly in ІІІ-IV stages of diseases...

Patients with mutations of WDR4, a substrate adaptor of the CUL4 E3 ligase complex, develop cerebellar atrophy and gait phenotypes. However, the underlying mechanisms remain unexplored. Here, we identify a crucial role of Wdr4 in cerebellar development. Wdr4 deficiency in granule neuron progenitors (GNPs) not only reduces foliation and the sizes of external and internal granular layers but also compromises Purkinje neuron organization and the size of the molecular layer, leading to locomotion defects. Mechanistically, Wdr4 supports the proliferation of GNPs by preventing their cell cycle exit...

Trisomy 21, the genetic cause of Down syndrome, disrupts primary cilia formation and function, in part through elevated Pericentrin, a centrosome protein encoded on chromosome 21. Yet how trisomy 21 and elevated Pericentrin disrupt cilia-related molecules and pathways, and the in vivo phenotypic relevance remain unclear. Utilizing ciliogenesis time course experiments combined with light microscopy and electron tomography, we reveal that chromosome 21 polyploidy elevates Pericentrin and microtubules away from the centrosome that corral MyosinVA and EHD1, delaying ciliary membrane delivery and mother centriole uncapping essential for ciliogenesis...

The human cerebellum contains more than 60% of all neurons of the brain. Anatomically, the cerebellum is divided into 10 lobules (I-X). The cerebellar cortex is arranged into three layers: the molecular layer (external), the Purkinje cell layer and the granular layer (internal). Purkinje neurons and interneurons are inhibitory, except for granule cells. The layer of Purkinje neurons inhibit cerebellar nuclei, the sole output of the cerebellar circuitry, as well as vestibular nuclei. The cerebellum is arranged into a series of olivo-cortico-nuclear modules arranged longitudinally in the rostro-caudal plane...

Background: Regeneration of injuries occurring in the central nervous system is extremely difficult. Studies have shown that the developing cerebellum can be repopulated by a group of Nestin-expressing progenitors (NEPs) after irradiation injury, suggesting that modulating the mobilization of NEPs is beneficial to promoting nerve regeneration. To date, however, effect of exogenous pharmaceutical agonist on NEPs mobilization remains unknown. Parthenolide (PTL), a sesquiterpene lactone isolated from shoots of feverfew...