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Cellular migration patterns in the developing mouse cerebral cortex.

The migration patterns of embryonic mouse cortical cells were investigated using a replication-incompetent retrovirus vector (BAG). The lateral ventricles of embryonic day 12 mouse embryos were infected with BAG and brains were harvested 2, 3, 4 and 6 days after infection. The location and morphology of all infected cortical cells were recorded from serial sections of entire brains, which were then reconstructed in three dimensions. Examination of the distribution of labelled cells revealed that there were migration patterns characteristic of each medial-lateral domain of the cortex. In the medial and dorsal areas, migration was often radial, although tangential spread increased with survival time, in large part due to ramification of cells in the intermediate zone. In the dorsolateral and lateral areas of the cortex, radial migration was generally not observed. Rather, variable extents of tangential migration occurred, and often resulted in wide separation of cells in the cortical plate. Almost all of the cellular dispersion occurred in the intermediate zone, although a modest degree of dispersion also occurred within the cortical plate itself. Most dispersion occurred in the mediolateral plane, with relatively little dispersion along the anteroposterior axis. Though characteristic migration patterns could be defined, wide variability in the extents of radial migration and tangential separation of cells was seen. The patterns of migration paralleled the distribution of radial glial fibers in all areas, and are most likely a reflection of the role of this network in supporting the migration of cortical neurons. The extent and variability of cellular dispersion supports a lineage-independent mechanism of cortical column ontogenesis.

Animals

A comparison of the migration patterns of normal and malignant cells in two assay systems.

The migration patterns of normal mouse embryo fibroblast (MEF) cells and mouse fibrosarcoma (FS) cells were compared in two assay systems. The two assay systems used were themodified Boyden chamber (micropore membrane) assay and the agarose drop explant assay. In both assays the major population of MEF cells exhibited a greater rate of migration than the major population of FS cells. However, a small subpopulation of FS cells which had a much greater rate of migration than the major population of either MEF or FS cells was detected in the agarose drop assay. A number of drugs which are known to inhibit the migration of leukocytes were tested against the MEF and FS cells. Concentrations were found that inhibited the major population of both groups by greater than 90%. However, at concentrations which inhibited the migration of the major population of FS cells by greater than 90%, a small group of fast-moving cells was still detected. Although the fast-moving cells were relatively resistant to treatment with the various drugs, this group was sensitive to a factor in serum. When normal human serum was used in place of fetal calf serum, the migration of the major population of FS cells was inhibited very little but movement of the fast-moving population was completely eliminated. We speculate that the small subgroup of fast-moving cells may be responsible for the invasive nature of the FS cells.

Blood

Migration patterns of donor astrocytes after reciprocal striatum-cerebellum transplantation into newborn hosts.

Fragments of striatum or cerebellum from E 25 rabbit embryo were implanted into either the striatum or the mesencephalon of newborn mice. Implanted rabbit astrocytes were selectively identified by monoclonal antibodies to the GFAP which are unable to combine with mouse GFAP. Previous investigations had shown that xenogenic astrocytes have the capacity to migrate in host CNS. The purpose of this study was to compare the patterns of migration of transplant-derived astroglial cells according to the topographic origin of the transplant and location of the grafting site. We found that the migration pattern of the grafted cells from any of both selected sites of implantation was independent from the topographic origin of the transplant. The routes as well as the distances of migration were similar after homo- or heterotopic transplantation. We conclude that astroglial cells or their precursors do not express information which would direct them to move specifically toward a defined region in the host brain according to the region of origin in the donor.

Animals

Migration patterns of sympathetic preganglionic neurons in embryonic rat spinal cord.

The displacement of immature neurons from their place of origin in the germinal epithelium toward their adult positions in the nervous system appears to involve migratory pathways or guides. While the importance of radial glial fibers in this process has long been recognized, data from recent investigations have suggested that other mechanisms might also play a role in directing the movement of young neurons. We have labeled autonomic preganglionic cells by microinjections of horseradish peroxidase (HRP) into the sympathetic chain ganglia of embryonic rats in order to study the migration and differentiation of these spinal cord neurons. Our results, in conjunction with previous observations, suggest that the migration pattern of preganglionic neurons can be divided into three distinct phases. In the first phase, the autonomic motor neurons arise in the ventral ventricular zone and migrate radially into the ventral horn of the developing spinal cord, where, together with somatic motor neurons, they form a single, primitive motor column (Phelps P. E., Barber R. P., and Vaughn J. E. (1991). J. Comp. Neurol. 307:77-86). During the second phase, the autonomic motor neurons separate from the somatic motor neurons and are displaced dorsally toward the intermediate spinal cord. When the preganglionic neurons reach the intermediolateral (IML) region, they become progressively more multipolar, and many of them undergo a change in alignment, from a dorsoventral to a mediolateral orientation. In the third phase of autonomic motor neuron development, some of these cells are displaced medially, and occupy sites between the IML and central canal. The primary and tertiary movements of the preganglionic neurons are in alignment with radial glial processes in the embryonic spinal cord, an arrangement that is consistent with a hypothesis that glial elements might guide autonomic motor neurons during these periods of development. In contrast, during the second phase, the dorsal translocation of preganglionic neurons occurs in an orientation perpendicular to radial glial fibers, indicating that glial elements are not involved in the secondary migration of these cells. The results of previous investigations have provided evidence that, in addition to glial processes, axonal pathways might provide a substrate for neuronal migration. Logically, therefore, it is possible that the secondary dorsolateral translocation of autonomic preganglionic neurons could be directed along early forming circumferential axons of spinal association interneurons, and this hypothesis is supported by the fact that such fibers are appropriately arrayed in both developmental time and space to guide this movement.

Animals

Migration patterns of dendritic cells in the rat: comparison of the effects of gamma and UV-B irradiation on the migration of dendritic cells and Lymphocytes.

To further define the underlying mechanisms of immune suppression induced by UV-B irradiation, we have examined the kinetics of homing patterns of in vitro UV-B-irradiated and gamma-irradiated-thoracic duct lymphocytes (TDL) compared to dendritic cells (DC). Our findings show that 111In-oxine-labeled TDL specifically home to the spleen, liver, lymph nodes, and bone marrow with subsequent recirculation of a large number of cells from the spleen to lymph nodes. In contrast, DC preferentially migrate to the spleen and liver with a relatively insignificant distribution to lymph nodes and an absence of subsequent recirculation. Splenectomy prior to cell injection significantly diverts the spleen-seeking DC to the liver but not to the lymph nodes, while the homing of TDL to lymph nodes is significantly increased. In vitro exposure of 111In-oxine labeled TDL to gamma irradiation does not significantly impair immediate homing to lymphoid tissues but inhibits cell recirculation between 3 and 24 hr. In contrast, gamma irradiation does not affect the tissue distribution of labeled DC, suggesting that DC are more radioresistant to gamma irradiation than TDL. Unlike the findings in animals injected with gamma-irradiated cells, UV-B irradiation virtually abolished the homing of TDL to lymph nodes and significantly reduced the homing of the spleen-seeking DC to the splenic compartment while a large number of cells were sequestered in the liver. The results of in vitro cell binding assay show that TDL, unlike DC, have the capacity to bind to high endothelial venules (HEV) within lymph node frozen sections while gamma and UV-B irradiation significantly inhibit the binding of TDL to lymph node HEV. These findings suggest that: (i) DC, unlike TDL, are unable to recirculate from blood to lymph nodes through HEV; (ii) although gamma irradiation impairs TDL recirculation, it does not affect DC tissue distribution; and (iii) UV-B irradiation impairs both TDL and DC migration patterns. We conclude that the lack of capacity of irradiated TDL to home to lymph nodes is due to damage to cell surface homing receptors and that the failure of DC to home to the lymph node microenvironment is related to the absence of HEV homing receptors on their cell surface.

Animals

T lymphocyte migration to arthritic joints and dermal inflammation in the rat: differing migration patterns and the involvement of VLA-4.

The migration of T lymphocytes into arthritic joints of rats with adjuvant arthritis was examined and compared to the accumulation of the same cells in cutaneous inflammation, since previous studies had shown that only a subpopulation of T lymphocytes, found enriched in peritoneal exudates (sPEL), migrated efficiently to cutaneous inflammatory sites. Surprisingly, lymphocyte migration to the inflamed joint included T cells from most of the recirculating lymphocyte pool, including sPEL, spleen, peripheral lymph node (PLN), and Peyer's patches, and was much more rapid than migration through either cutaneous sites or PLNs. Treatment of sPEL with antibody to VLA-4 inhibited sPEL accumulation in the joints, while anti-VLA-4 treatment did not affect the accumulation of PLN T cells. It is concluded that the arthritic joint not only attracts inflammation-seeking lymphocytes (sPEL), through at least a partially VLA-4 dependent interaction, but also large numbers of lymphocytes which normally migrate to PLNs through a VLA-4-independent mechanism.

Animals

On the development of the cerebellum of the trout, Salmo gairdneri. I. Patterns of cell migration.

Patterns of cell migration in the cerebellum of Salmo gairneri RICHARDSON, 1836 were studied in fish ranging in length from 4.5 to 230 mm. Sagittal and transverse series were stained with haematoxylin-eosin or according to Nissl or Golgi. The cerebellum of the trout comprises three main parts, i.e. the massive corpus cerebelli, the folded valvula cerebelli and the transversely oriented lobus vestibulolateralis. The early cerebellar anlage is a simple plate, which is delimited from the tectum mesencephali by the fissura rhombo-mesencephalica. The histogenesis may be divided into three phases. During the first phase the matrix layer produces the mantle layer. During the second phase the three typical cerebellar layers are formed. The third phase is characterized by growth. As regards the first phase, the mantle layer develops throughout almost the entire extent of the cerebellar anlage. Only in a narrow paramedian strip (matrix zone M) this layer does fail to appear. In regions where the mantle layer is formed, the matrix no longer occupies the whole width of the wall and is termed the ventricular matrix. The largest part of the ventricular matrix is gradually exhausted. However, in some places this matrix persists as a layer of proliferating cells. This holds for the matrices of the caudal border of the cerebellum; matrix zone L, surrounding the lateral recesses of the fourth ventricle, and matrix zone P, connecting the matrix zones L. The mantle layer produced in the first phase of histogensis mainly develops into the ganglionic layer. The second phase of histogenesis is characterized by the formation of a secondary matrix. Newly produced cells of the matrix zones M, L and P migrate away from their sites of origin towards the regions where a mantle layer prevsiously has been formed. The majority of these cells develops into granule cells. Migration of the cells produced in the first phase of histogenesis occurs in the radial direction. Because of the curvature of the cerebellum this direction changes with respect to the main longitudinal axis of the brain from region to region. The migration paths of granule cells show variable directions, namely (a) tangential followed by radial, for granule cells in the corpus cerebelli and in the medial parts of the valvula cerebelli and the lobus vestibulolaterialis, (b) tangential, for granule cells in the lateral parts of the valvula and (c) radial, for granule cells in the lateral parts of the lobus vestibulolateralis. The analysis of these migration patterns elucidates both the histogenesis and the morphogenesis of the cerebellum of the trout.

Animals

Aberrant lymphocyte migration patterns in systemic lupus erythematosus (MRL/l, MRL/n) mice are independent of the micro-environment.

Mice with systemic lupus erythematosus (SLE) have unusual patterns of lymphocyte traffic characterised by diminished uptake of intravenously injected autoimmune cells into lymph nodes. This study examines the influence of the lymphocyte micro-environment on this aberrant migratory behaviour. To evaluate lymph node lymphocyte-endothelial interactions which can affect lymphocyte distribution without the in vivo influence of liver and spleen, the in vitro high endothelial venule (HEV) binding assay was used. Lymph node HEV binding of autoimmune MRL-lpr/lpr (MRL/l) and MRL(-)+/+ (MRL/n) lymphocytes was increased when compared with CBA/T6 lymphocytes and contrasted with diminished lymph node uptake noted in vivo. This was independent of the lymph node source (MRL/l, MRL/n, CBA/T6) onto which the lymphocytes were overlaid. To examine the influence of the microenvironment on in vivo traffic, 21Cr-labelled lymph node cells from normal CBA/T6 mice were injected into sex-matched MRL/l, MRL/n and CBA/T6 recipients. The distribution of cells was the same in each recipient strain suggesting that the micro-environment had little influence on the lymphocyte trafficking profiles of autoimmune mice. This study supports the view that aberrant lymphocyte migration in autoimmune mice results from defects intrinsic to the lymphocyte population and not the micro-environment.

Age Factors

Migration pattern of splenic lymphocytes after local labelling of the pig spleen with 3H-cytidine.

In normal young pigs splenic lymphocytes were selectively labelled by injecting tritiated cytidine into a splenic artery. 10 h later several lymphoid and non-lymphoid organs were investigated for spleen-derived lymphocytes by autoradiography. The relative and absolute organ distribution of the labelled cells was determined. Labelled lymphocytes appeared rapidly in the peripheral blood reaching a mean labelling index of 4.8%. More splenic lymphocytes were found in thymus dependent areas than in thymus independent areas of lymphoid organs. Nearly 40% of all emigrated lymphocytes homed to lymph nodes and only about 1% in the thymus. A surprisingly high number of splenic lymphocytes were located in the bone marrow and the lung.

Animals

A longitudinal radiographic study of the periosteal migration along the growing rabbit mandible.

In the present study, the role of the periosteum in mandibular growth was investigated. The orientation of the superficial bony spicules of rabbit mandibles was determined on dry skulls after perfusion of the animals with an India ink solution. The spicular orientation in the ramus area appeared to be toward the condyle, rostrally toward the incisors, and caudally toward the angular region. The behavior, during growth, of the periosteum in the caudal mandibular half was studied by implantation of metal periosteal and bone markers. A series of cephalograms revealed the migration pattern of the periosteal markers, and by that the migration pattern of the periosteum. It can be concluded that both the pattern of the superficial bony spicules and the periosteal migration pattern suggest a possible influence of the periosteum on mandibular growth.

Animals

Modulation of B cell maturation and migration to the thymus of SJL mice. B cell migration to the thymus.

The direct linkage of the B cell maturation process and infiltration of the thymus with mature B cells was studied in SJL mice. Phenotypically and functionally, B cells in the thymus of old SJL mice are mature B cells; IgM+, IgD+, Ly-1-, and evince a high proliferative response to lipopolysaccharide and a low one to dextran sulphate. Memory B cells can be found in the thymus of mice immunized with T-dependent or T-independent antigens. Chronic depletion and B cell maturation arrest induced by fractionated total lymphoid irradiation or by neonatal splenectomy eliminate B cells from the thymus and block their migration from the periphery to the thymus. When examined in adoptive transfer experiments, thymus B cells were found to possess a normal migration pattern and homing receptors; their migration pattern did not differ from that of lymph node or splenic B cells. It is evident, therefore, that the large number of normal functioning B cells in the thymus of SJL mice reflects a massive infiltration of the thymus by mature B cells from the periphery due to thymus dysfunction rather than to an abnormal in situ differentiation of intrathymic B cell precursors.

Animals