PubMed Health⌕ Search

Biomedical subjects

A Goffinet

Publications and source records attributed to A Goffinet.

16 recordsLinked to original sources
PubMed2001

Axonal secretion of Reelin by Cajal-Retzius cells: evidence from comparison of normal and Reln(Orl) mutant mice.

A novel secretory pathway has been identified in the study of mice homozygous for the Reln(Orl) mutation, a line characterised by the defective secretion of the large extracellular matrix glycoprotein Reelin. By using both light and electron microscopy, immunohistochemical studies for Reelin in these mutants identified morphological changes in their Cajal-Retzius cells (CR cells). The CR cells of the mutant displayed the characteristic features of bipolar, tangentially elongated neurons with a dendritic proximal pole and an axonal cone at the opposite end of the soma. At either pole, cisterns of prominent rough endoplasmic reticulum (RER) were found to be rich in Reelin. However, the Reelin-positive RER cisterns of the axonal cones were hugely dilated in homozygous Reln(Orl) mice as compared with their wild type counterparts. CR cell axons displayed beads throughout their length, each contained a smooth spheroidal cistern filled with Reelin-immunoreactive fibrillar material, and were increased in number and size in Reln(Orl) mice. RER phenotype was rescued in the Reln(Alb2) mice, a mutation in which no Reelin protein is produced. We propose that the RER dilations viewed in the Reln(Orl) mutation are due to the accumulation of the defective Reelin protein, and the large axonal beads in Reln(Orl) mice reflect the accumulation of truncated Reelin as the result of defects in its secretion. These observations point to an original, hitherto unrecognised, mechanism of secretion by bulk transport in smooth cisterns from the axonal cone into the axon, followed by secretion in the cortical marginal zone from the axonal cisterns that we have named axonal reelin reservoirs.

Acetylcholine↗
PubMed2001

Pre- and post-mitotic events contribute to the progressive acquisition of area-specific connectional fate in the neocortex.

The adult primary motor cortex (area 6) is characterized by a stronger projection to the spinal cord than the primary somatosensory cortex (area 3). Here we have explored the progressive and regressive phenomena that determine these areal differences in the number of corticospinal neurons (CSNs). CSNs were birthdated with [(3)H]thymidine and subsequently retrogradely labeled from the spinal cord. The time window of CSN production is identical in both areas. The probability that a cohort of neuroblasts project to the spinal cord is indicated by the percentage of [(3)H]thymidine-positive neurons that can be back-labeled from the spinal cord. In the neonate this fate index is significantly higher in area 6 compared with area 3, indicating that early regionalization of cell fate contributes to areal differences in CSN number. In neonatal reeler mice, an increase in CSN number was accompanied by an increased fate index, showing that the integrity of the post-mitotic environment is required for the specification of the appropriate number of neurons expressing a given connectional phenotype. Postnatal development in reeler and normal is characterized by an area-specific elimination of CSN axons, which reduces areal differences in CSN number. These results show a progressive acquisition of CSN fate in the neocortex and indicate that both early regionalization and late environmental signals contribute to determining areal differences of connectional phenotype.

Animals↗
PubMed1999

Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation.

The large extracellular matrix protein Reelin is produced by Cajal-Retzius neurons in specific regions of the developing brain, where it controls neuronal migration and positioning. Genetic evidence suggests that interpretation of the Reelin signal by migrating neurons involves two neuronal cell surface proteins, the very low density lipoprotein receptor (VLDLR) and the apoE receptor 2 (ApoER2) as well as a cytosolic adaptor protein, Disabled-1 (Dab1). We show that Reelin binds directly and specifically to the ectodomains of VLDLR and ApoER2 in vitro and that blockade of VLDLR and ApoER2 correlates with loss of Reelin-induced tyrosine phosphorylation of Disabled-1 in cultured primary embryonic neurons. Furthermore, mice that lack either Reelin or both VLDLR and ApoER2 exhibit hyperphosphorylation of the microtubule-stabilizing protein tau. Taken together, these findings suggest that Reelin acts via VLDLR and ApoER2 to regulate Disabled-1 tyrosine phosphorylation and microtubule function in neurons.

Animals↗
PubMed1993

Presence of growth hormone-binding proteins in cattle plasma and milk.

The presence of GH-binding proteins (GHBPs) in the plasma of adult cattle was investigated using Sephadex G-200 filtration, Western ligand blotting and Western blotting. The changes in the concentration of GHBP in the plasma of dairy half-sister heifers during the first year of life as well as the presence of GHBP in milk were also investigated. When analytical chromatography (on a 1.6 x 100 cm column) was performed, five peaks of recombinant bovine GH (rbGH)-associated radioactivity were revealed in cattle plasma; the first peak, which appeared near the void volume, was presumed to represent aggregates, the second (M(r) 290 kDa) and the third peaks (M(r) 75 kDa) corresponded to specific rbGH-GHBP complexes; the last two peaks representing free 125I-labelled rbGH and Na[125I]. Western ligand blotting revealed multiple GHBPs. Three major bands were observed at approximately 190, 58 and 31 kDa; an excess of unlabelled hormone blocked the binding of 125I-labelled rbGH. Minor non-specific binding bands were also detected in cattle plasma with molecular weights between 40 and 136 kDa. One monoclonal antibody (8H7) produced against synthetic peptide (amino acids 54-63 of the extracellular domain of the bovine GH receptor) specifically interacted with 190 and 58 kDa bands while the 31 kDa band was not recognized. Finally, Western ligand blots were performed to evaluate the changes in plasma GHBP during the first year of life in 55 dairy half-sister heifers and to identify GHBP in milk. In plasma, the intensity of the 31 kDa band varied greatly between animals while the other specific bands remained stable.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

High metabolic activity in the visual cortex of early blind human subjects.

Glucose metabolism has been studied in the visual cortex of early blind human subjects. In the forebrain of these subjects, regional glucose utilization was the highest in the striate and prestriate cortical areas. Furthermore, this activity was higher than in blindfolded sighted subjects, whether at rest or during an auditory or tactile task. These observations raise the question of the functionality of the blind's visual cortex.

Blindness↗
PubMed1987

Leukotriene C4 binding sites in mouse brain: pharmacological characteristics.

The binding sites for [3H]leukotriene C4 were studied in membrane preparations of mouse brain and liver. Isotherm binding analysis revealed one binding site with a Kd of 10.39 +/- 1.97 nM (Scatchard) or 10.15 +/- 1.00 nM (non-linear). The maximal binding capacity (Bmax) was 49.20 +/- 3.80 (Scatchard) or 48.50 +/- 2.63 (non-linear) pmol/mg prot. Specific binding represented more than 90% of the total binding. In displacement reactions on brain membranes, LTC4 was 100 times more active than LTD4, which displayed 10 times the activity of GSH. Glutamic acid, bilirubin and hematin were inactive. The activity of LTC4 was slightly less on liver membranes than on brain membranes. Liver sites had some affinity for GSH but not for LTD4 bilirubin or hematin. The results support the hypothesis that LTC4 and its receptor may have a neuromodulatory function.

Animals↗
PubMed1985

Laminar distribution of alpha 1- and beta 1-adrenoceptors in ferret visual cortex.

The distribution of alpha 1- and beta 1-adrenoceptors has been examined in the ferret visual cortex (area 17), with an autoradiographic procedure using iodine-125 labeled hydroxy-iodophenyl-ethylaminomethyl-tetralone (HEAT) and iodocyanopindolol (ICYP), respectively. The density of ligand binding with ICYP, known to have selective affinity for beta-receptors, was heavy over layers I-III, very low over layer IV, and medium over V and VI. In contrast, binding sites for HEAT, a new ligand selective for alpha-receptors, were diffusely distributed, although preferentially concentrated in layer IV and the upper layers. The distinct laminar distribution of these two receptor types may imply two cortical channels for norepinephrine influence; alpha 1-receptors may be preferentially associated with enhancement of excitatory inputs to layer IV; beta 1-receptors, in contrast, with enhancement of inhibitory responses outside layer IV.

Adrenergic Fibers↗
PubMed1982

Ependymitis, leukoencephalitis, hydrocephalus, and thrombotic vasculitis following chronic infection by mouse hepatitis virus 3 (MHV 3).

Mouse hepatitis virus 3 (MHV 3) is either avirulent (resistant mice), hepatotropic (susceptible mice), or neurotropic (semisusceptible mice), depending on the strain of mice infected. In semisusceptible mice, infection led first to a transient meningitis, ependymitis, and leukoencephalitis, followed by a permanent communicating hydrocephalus and, later on, to a chronic thrombotic vasculitis affecting meningeal and parenchymal vessels at the brain stem level. Small foci of ischemic necrosis related to vascular occlusions were seen in the dorsal brain stem. Cyclophosphamide treatment of semisusceptible mice significantly reduced the meningeal infiltrates but did not prevent the development of hydrocephalus and other neuropathologic changes. Identical lesions occurred in fully susceptible mice infected with a low dose of virus, but no neurologic disorder could be induced in genetically resistant mice even following immunosuppression or intracranial inoculation. The leukoencephalitis differed from the demyelinating lesions observed with MHV 4. Vascular lesions were of particular interest. More attention should be given to the possibility of virus induced chronic cerebral vasculitis in man.

Animals↗
PubMed1981

Inverted pyramidal neurons and their axons in the neocortex of reeler mutant mice.

Inverted pyramidal neurons are very abundant in the cerebral cortex of the adult reeler mutant mouse. Two types of inverted pyramid are found in rapid Golgi impregnations. In the first type the axon starts from the base of the cell body and bends towards the white matter. In the second type, which is more common, the axon emerges from the apical dendritic tree and descends directly towards the white matter. Despite its abnormal topography, the site of origin of the axon in pyramids of the second type displays a normal differentiation, when analysed with the electron microscopic Golgi technique, suggesting that the ectopic initial axon segment is able to fulfil its normal functions.

Animals↗
PubMed1981

Formation of "neo-cortex" in a congenital human teratoma.

A congenital human teratoma contained a neuroectodermal mass with architectonic features similar to those of the normal developing neo-cortex. Surrounding a central cavity, a germinal, an intermediate and a cortical zone were clearly distinguishable from innermost to outermost. Glial fibers coursed radially through the intermediate and cortical zones. In the "cortical plate" neuronal elements were oriented radially with an inside out gradient of differentiation. Mesothelial tissue covered the outer surfaces of the "cortex". Over limited sectors a gap in the integrity of the meso-glial barrier were associated with neuroglial ectopias. The following points are of neurobiologic importance: the information of the "miniature cerebral cortex" occurred in the absence of any influence of afferent subcortical fibers. The radial alignment of glial fibers between the germinal pseudostratified epithelium and the outer surface occurred only in sectors of the neuroectodermal mass where a "neo-cortex" was present, and may therefore have been a critical determinant in the formation of the "cortical plate". The integrity of the outer glial mesenchymal barrier may be necessary for the normal arrangement of cortical neurons.

Brain Neoplasms↗
PubMed1979

Mitotic spindle fiber orientation in relation to cell migration in the neo-cortex of normal and reeler mouse.

The angular distribution of mitotic spindle fibers has been studied in the telencephalic ventricular zone (VZ) of mouse embryos and has been found to be monophasic and invariant during the early cortical histogenesis both in the normal and in a reeler embryo. This observation suggests that the orientation of mitotic spindle fibers is independent of nerve cell migration in the embryonic cortex.

Animals↗
PubMedDate not supplied

[Early histogenesis in the cerebral cortex of the mouse: a Golgi analysis (author's transl)].

By the application of the rapid Golgi method to embryonic telencephalon, three stages can be distinguished in the early developmznt of the neocortex. Stage 1 is characterized by a neuroepithelium containing a continuously proliferating cell population. Stage 2 corresponds to the primordial cortical organization; the first neuronal (post-mitotic) cells appear in the external part of the neural tube and are differentiated in a predominantly horizontal pattern. Stage 3 begins when the cortical plate appears. This structure will give rise to the major part of the adult cortex. The cells of the cortical plate assume a typical radial orientation and their axons (afferent fibers) are well individualized. The afferent fibers however, are not easily analyzed by the technique employed. Those morphological findings are discussed in relation to various data from the literature in developmental neurology.

Animals↗