scholarly journals QUANTITATIVE ANALYSIS OF CELL PROLIFERATION AND DIFFERENTIATION IN THE CORTEX OF THE POSTNATAL MOUSE CEREBELLUM

1967 ◽  
Vol 32 (2) ◽  
pp. 277-287 ◽  
Author(s):  
Setsuya Fujita
Keyword(s):  
Granular Layer ◽  
Molecular Layer ◽  
External Granular Layer ◽  
Proliferating Cells ◽  
Daily Production ◽  
Cell Proliferation And Differentiation ◽  
Matrix Cell ◽  
Proliferation And Differentiation ◽  
Before And After ◽  
Mantle Layer

The generation cycle of germinative cells (external matrix cells) in the external granular layer of the cerebellar cortex of the 10-to 11-day-old mouse was studied by radioautography following repeated injections of H3-thymidine. The generation time is 19 hr, presynthetic time 8.5 hr, DNA-synthetic time 8 hr, postsynthetic time 2 hr, and mitotic time 0.5 hr. These proliferating cells occupy the outer half of the external granular layer and make up the external matrix layer. Neuroblasts are differentiated from the external matrix cell, migrate out from the layer and accumulate in the inner half of the external granular layer to form the external mantle layer. The transit time of the neuroblasts in the external mantle layer is 28 hr. Thereafter, they migrate farther into the molecular layer and the internal granular layer. By means of long-term cumulative labeling, the rate of daily production of neuroblasts from the external matrix cell is studied in quantitative terms. It becomes clear that the entire population of the inner granule neurons arises postnatally in the external granular layer between 1 and 18 days of age and that 95% of them is produced between postnatal days 4 and 15. Finally, the fate of the cells in the external granular layer at its terminal stage was studied by marking the cells with H3-thymidine during 15–16 days of life and following their subsequent migration and developmental changes up to 21 days of life. Comparison of radioautographs taken before and after the migration disclosed that the external matrix cells give rise to a small number of neuroglia cells. This finding revealed their multipotential nature.

Contrasting patterns of c-myc and N-myc expression in proliferating, quiescent, and differentiating cells of the embryonic chicken lens

Development ◽  
1992 ◽  
Vol 115 (3) ◽  
pp. 813-820
Author(s):  
L.L. Harris ◽  
J.C. Talian ◽  
P.S. Zelenka
Keyword(s):  
Cell Proliferation ◽  
Protein Product ◽  
Mrna Levels ◽  
Lens Fiber ◽  
Proliferating Cells ◽  
Fiber Cells ◽  
Embryonic Chicken ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

The present study uses the polymerase chain reaction and in situ hybridization to examine c-myc and N-myc mRNA in the embryonic chicken lens at 6, 10, 14 and 19 days of development and compares the pattern of expression obtained with the developmental pattern of cell proliferation and differentiation. In the central epithelium, c-myc mRNA levels were proportional to the percentage of proliferating cells throughout development. N-myc mRNA expression in this region was relatively low and showed no correlation with cell proliferation. The ratio of N-myc to c-myc mRNA increased markedly with the onset of epithelial cell elongation and terminal fiber cell differentiation, although both c-myc and N-myc mRNAs continued to be expressed in postmitotic, elongating cells of the equatorial epithelium and in terminally differentiating lens fiber cells. Thus, increased expression of N-myc, a gene whose protein product may compete with c-myc protein for dimerization partners, accompanies the dissociation of c-myc expression and cell proliferation during terminal differentiation of lens fiber cells.

scholarly journals Prenatal treatment with metronidazole induces cerebellar folia alteration in guinea pig fetuses

2020 ◽  
Vol 72 (4) ◽  
pp. 473-482
Author(s):  
Ivan Capo ◽  
Ivan Milenkovic ◽  
Natasa Capo ◽  
Nebojsa Stilinovic ◽  
Sasa Vukmirovic ◽  
...  
Keyword(s):  
Animal Studies ◽  
Granular Layer ◽  
Molecular Layer ◽  
Sensitive Period ◽  
Insufficient Data ◽  
Prenatal Treatment ◽  
External Granular Layer ◽  
Areal Fraction ◽  
Experimental Group ◽  
Partial Atrophy

The most sensitive period in brain development is during prenatal life. The use of antibiotics in pregnancy is still controversial. Recent studies revealed the high neurotoxic potential of the antibiotic and antiprotozoal medication, metronidazole. However, there are insufficient data from animal studies about prenatal treatment effects. We investigated the effect of prenatal treatment with metronidazole on cerebellar development in guinea pigs. Treatment with metronidazole was performed from the 42nd to the 49th day of gestation. On the 50th day of pregnancy, all dams were killed, and the cerebella of the fetuses were analyzed. Gross cerebellar changes characterized by malposition of the folia with partial atrophy were found in 12 of 19 fetuses in the experimental group, but in none of 20 control fetuses that received saline. The most affected were folia VII with depletion of the areal fraction of the external granular layer, molecular layer and the internal granular layer. Purkinje cells displayed cell distortion with loss of normal dendritic polarity. The investigation revealed cell depletion, with a disturbance of the cytoarchitectonic of the cerebellar cortex and folia alteration.

scholarly journals Ultrastructural study of proliferating cells with an improved immunocytochemical detection of DNA-incorporated bromodeoxyuridine.

1995 ◽  
Vol 43 (1) ◽  
pp. 21-29 ◽  
Author(s):  
R Tamatani ◽  
Y Taniguchi ◽  
Y Kawarai
Keyword(s):  
Ultrastructural Study ◽  
Staining Method ◽  
Improved Method ◽  
Proliferating Cells ◽  
Gold Particles ◽  
Immunocytochemical Detection ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Silver Staining Method ◽  
Incorporated Brdu

We designed an improved method to observe proliferating cells with well-preserved ultrastructure. After IP injection of bromodeoxyuridine (BrdU) into rats, the pituitaries were fixed in 4% paraformaldehyde with 0.05% or 0.2% glutaraldehyde and post-fixed with ferrocyanide-reduced osmium. They were embedded in LR White and polymerized by heat. BrdU incorporated into DNA was detected with a commercial anti-BrdU monoclonal antibody (MAb) by the immunogold or the immunogold-silver staining method. Using these methods, proliferating cells labeled by BrdU were observed with well-preserved ultrastructure. By light microscopy, the number of labeled cells was almost the same regardless of the fixative used. By electron microscopy, localization of gold particles that indicate incorporated BrdU varied according to the cells and was mainly observed in two patterns, one in which gold particles were localized in condensed chromatin scattered in the nucleus and the other in which gold particles were dispersed evenly all over the nucleus. These results showed that with our improved method fine ultrastructure and good immunoreactivity of BrdU can be obtained in proliferating cells. We consider that this method is very useful for ultrastructural study of cell proliferation and differentiation.

Blood activation and compatibility on single-molecular-layer biointerfaces

2014 ◽  
Vol 2 (30) ◽  
pp. 4911-4921 ◽  
Author(s):  
Shengqiang Nie ◽  
Hui Qin ◽  
Chong Cheng ◽  
Weifeng Zhao ◽  
Shudong Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Molecular Layer ◽  
Artificial Organs ◽  
Living Systems ◽  
Tissue Cultures ◽  
Stem Cell Proliferation ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Single Molecular Layer

Research on the interactions between living systems and materials is fuelled by diverse biomedical needs, for example, drug encapsulation and stimulated release, stem cell proliferation and differentiation, cell and tissue cultures, as well as artificial organs.

A new approach to the development of the cerebellum provided by the quail-chick marker system

Development ◽  
1990 ◽  
Vol 108 (1) ◽  
pp. 19-31 ◽  
Author(s):  
M.E. Hallonet ◽  
M.A. Teillet ◽  
N.M. Le Douarin
Keyword(s):  
Granular Layer ◽  
Sagittal Plane ◽  
Molecular Layer ◽  
Purkinje Neurons ◽  
Small Cells ◽  
Cell Type ◽  
External Granular Layer ◽  
Morphogenetic Movements ◽  
Cellular Marker ◽  
Cerebellar Cells

We have used the quail-chick chimera system to reveal the cell migrations and settling pattern involved in the construction of the cerebellum. Three types of orthotopic transplantations were carried out, between quail and chick embryos, at the 12-somite stage: exchanges of (i) the whole metencephalic vesicle, (ii) the lateral half of this vesicle and (iii) the diencephalic plus the mesencephalic vesicles. Histological study of chimeric embryos and young chicks provided the following results: longitudinal morphogenetic movements distort the embryonic neural tube as early as the fifth embryonic day, so that the dorsal limit of the mes-, met- and myelencephalic vesicles are displaced caudad and their ventral limits rostrad. This leads to a participation of mesencephalic vesicular material in the construction of the cerebellum. Cells originating in the mesencephalic vesicle are found in a rostromedial V-shaped region, in all the cerebellar cellular layers, except the external granular layer, the presumptive territory of which is entirely located in the metencephalic vesicle. The chimerism of the rostromedial part of the cerebellum allows the analysis of the origin of the various cerebellar cell types. We find (i) that the Purkinje cells always have the same cellular marker as the ventricular epithelium radially beneath them. This strongly suggests that these cells reach their final localization following strictly radial migrations. (ii) Most of the small cells surrounding the Purkinje neurons and most of the neurons and glial cells of the molecular layer are also of the same type as the ventricular epithelium they surmount, i.e. different from the type of the external granular layer cells. Therefore, they are not derived from the external granular layer and are not of the same origin as the granule cells as previously believed. Unilateral substitutions of the metencephalic vesicle revealed that transverse cell migrations occur across the sagittal plane. They have been observed mainly in the inner and external granular layers, but also, though to a lesser extent, in the molecular layer and in the cell layer located at the level of the Purkinje neurons. These observations show that the position of cerebellar cells is determined by both morphogenetic movements and cell type-specific active radial and tangential migrations. The quail-chick chimera system is thus able to provide new information both on the origin of cerebellar cells and how each cell type assumes its final position.

scholarly journals Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum

2000 ◽  
Vol 14 (8) ◽  
pp. 994-1004 ◽  
Author(s):  
Silvia Marino ◽  
Marc Vooijs ◽  
Hanneke van der Gulden ◽  
Jos Jonkers ◽  
Anton Berns
Keyword(s):  
Tumor Suppressor Genes ◽  
Granular Layer ◽  
Molecular Layer ◽  
Precursor Cells ◽  
Loss Of Function ◽  
External Granular Layer ◽  
Embryonal Tumors ◽  
Mortality And Morbidity ◽  
Null Mutant Mice ◽  
Developing Cerebellum

Medulloblastomas are among the most common malignancies in childhood, and they are associated with substantial mortality and morbidity. The molecular pathogenesis as well as the ontogeny of these neoplasms is still poorly understood. We have generated a mouse model for medulloblastoma by Cre–LoxP-mediated inactivation ofRb and p53 tumor suppressor genes in the cerebellar external granular layer (EGL) cells. GFAP–Cre-mediated recombination was found both in astrocytes and in immature precursor cells of the EGL in the developing cerebellum.GFAP–Cre;RbLoxP/LoxP;p53−/−or LoxP/LoxP mice developed highly aggressive embryonal tumors of the cerebellum with typical features of medulloblastoma. These tumors were identified as early as 7 weeks of age on the outer surface of the molecular layer, corresponding to the location of the EGL cells during development. Our results demonstrate that loss of function of RB is essential for medulloblastoma development in the mouse and strongly support the hypothesis that medulloblastomas arise from multipotent precursor cells located in the EGL.

scholarly journals Subcellular Localization of Prolyl Endopeptidase During the First Wave of Rat Spermatogenesis and in Rat and Human Sperm

2018 ◽  
Vol 67 (4) ◽  
pp. 229-243 ◽  
Author(s):  
Massimo Venditti ◽  
Sergio Minucci
Keyword(s):  
Sertoli Cells ◽  
Cognitive Disorders ◽  
Human Sperm ◽  
Prolyl Endopeptidase ◽  
Peptidase Activity ◽  
Female Reproduction ◽  
Proliferating Cells ◽  
Cell Proliferation And Differentiation ◽  
Potential Association ◽  
Proliferation And Differentiation

Prolyl endopeptidase (PREP) is an enzyme which cleaves several peptide hormones and neuropeptides on the carboxyl side of proline residues and is involved in many biological processes, including cell proliferation and differentiation, glucose metabolism, learning, memory, and cognitive disorders. PREP has also been identified as a binding partner of tubulin, suggesting the involvement of endopeptidase in microtubule-associate processes, independent of its peptidase activity. Furthermore, several reports have implied PREP participation in both male and female reproduction-associated mechanism. We herein assess a potential association of PREP to the morphogenesis of rat testis, profiling its localization versus tubulin, during the first wave of spermatogenesis and in the adult gonad (from 7 to 60 dpp). We show that, in mitotic phases, PREP shares its localization with tubulin in Sertoli cells, gonocytes, and spermatogonia. Later, during meiosis, both proteins are found in spermatocytes, and in the cytoplasm of Sertoli cells protrusions, surrounding the germ cells, while, during spermiogenesis, they both localize in the cytoplasm of round and elongating spermatids. We also found that this enzyme has a peculiar nuclear localization, in the proliferating cells in all phases of analysis. Finally, they are expressed in the flagellum of mature gametes, as corroborated by additional immunolocalization analysis on both rat and human sperm. Our data support the hypothesis of the fundamental role of PREP in reproduction and in cytoskeletal organization during mammalian testis morphogenesis and gamete progression.

scholarly journals Sequential expression and differential function of multiple adhesion molecules during the formation of cerebellar cortical layers.

1987 ◽  
Vol 104 (2) ◽  
pp. 331-342 ◽  
Author(s):  
C M Chuong ◽  
K L Crossin ◽  
G M Edelman
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Granule Cell ◽  
Cell Adhesion Molecule ◽  
Granular Layer ◽  
Molecular Layer ◽  
External Granular Layer ◽  
Cortical Layers

We have correlated the times of appearance of the neural cell adhesion molecule (N-CAM), the neuron-glia cell adhesion molecule (Ng-CAM), and the extracellular matrix protein, cytotactin, during the development of the chicken cerebellar cortex, and have shown that these molecules make different functional contributions to granule cell migration. Immunofluorescent staining showed distinct spatiotemporal expression sequences for each adhesion molecule. N-CAM was present at all times in all layers. However, the large cytoplasmic domain polypeptide of N-CAM was always absent from the external granular layer and was enriched in the molecular layer as development proceeded. Ng-CAM began to be expressed in the premigratory granule cells just before migration and later disappeared from cell bodies but remained on parallel fibers. Cytotactin, which is synthesized by glia and not by neurons, appeared first in a speckled pattern within the external granular layer and later appeared in a continuous pattern along the Bergmann glia; it was also enriched in the molecular layer. After we established their order of appearance, we tested the separate functions of these adhesion molecules in granule cell migration by adding specific antibodies against each molecule to cerebellar explant cultures that had been labeled with tritiated thymidine and then measuring the differential distribution of labeled cells in the forming layers. Anti-N-CAM showed marginal effects. In contrast, anti-Ng-CAM arrested most cells in the external granular layer, while anti-cytotactin arrested most cells in the molecular layer. Time course analyses combined with sequential addition of different antibodies in different orders showed that anti-Ng-CAM had a major effect in the early period (first 36 h in culture) and a lesser effect in the second part of the culture period, while anti-cytotactin had essentially no effect at the earlier time but had major effects at a later period (18-72 h in culture). The two major stages of cerebellar granule cell migration thus appear to be differentially affected by distinct adhesion molecules of different cellular origins, binding mechanisms, and overall distributions. The results indicated that local cell surface modulation of adhesion molecules of different specificities at defined stages and sites is essential to the formation of cerebellar cortical layers.

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