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C Ffrench-Constant

Publications and source records attributed to C Ffrench-Constant.

13 recordsLinked to original sources
PubMed1991

Response to fibronectin of mouse primordial germ cells before, during and after migration.

The adhesive extracellular matrix glycoprotein fibronectin is thought to play a central role in cell migration during embryogenesis. In order to define this role, we have examined the response to fibronectin in cell culture of mouse primordial germ cells (PGCs) before, during and after their migration from the hindgut into their target tissue, the genital ridges. Using an explant culture system, we show that PGCs will emigrate from tissue fragments containing hindgut, and that fibronectin stimulates this migration. Adhesion assays show that the start of PGC migration is associated with a fall in adhesion to fibronectin. Double-labelling studies using in situ hybridization and histochemistry demonstrate that migrating PGCs do not contain detectable fibronectin mRNA, suggesting that they do not synthesize and secrete the fibronectin within their migratory substratum. Taken together, these findings are consistent with an important role for fibronectin in stimulating PGC migration. In addition, however, they suggest that the interaction between PGCs and fibronectin may be important in timing the start of migration, with the fall in adhesion allowing the PGCs to commence their migration towards the genital ridges.

Animals↗
PubMed1990

Requirements for integrins during Drosophila development.

The common beta subunit of the PS antigens of Drosophila is homologous with vertebrate integrins and is encoded by the lethal(1)myospheroid gene. We have generated flies mosaic for wild-type and mutant alleles of lethal(1)myospheroid using adult gynandromorphs and radiation-induced somatic crossing over. The defects observed in the gynandromorphs demonstrate widespread requirements for PS integrins during development especially in ventrally derived structures, which also show strong expression of PS beta integrin. Smaller lethal(1)myospheroid clones induced during larval development result in blister and vein defects in the wings and aberrant development of photoreceptor cells, demonstrating roles for PS integrins during development of both wings and eyes. PS integrins are required for the close apposition of the dorsal and ventral wing epithelia and for the proper arrangement of photoreceptor cells. However, many other adhesive and morphogenetic processes proceed normally in the absence of integrins containing the beta subunit encoded by lethal(1)myospheroid.

Animals↗
PubMed1989

Reappearance of an embryonic pattern of fibronectin splicing during wound healing in the adult rat.

The adhesive extracellular matrix glycoprotein fibronectin (FN) is thought to play an important role in the cell migration associated with wound healing. Immunolocalization studies show abundant FN in healing wounds; however, these studies cannot define the cellular site(s) of FN synthesis, nor do they distinguish the different and potentially functionally distinct forms of FN that can arise from alternative splicing of the primary gene transcript. To examine these questions of FN synthesis and splicing during wound healing, we have performed in situ hybridization with segment-specific probes on healing wounds in adult rat skin. We find that the FN gene is expressed at increased levels after wounding both in the cells at the base of the wound and in subjacent muscle and dermis lateral to the wound. Interestingly, however, the pattern of splicing of FN mRNA was different in these areas. In adjacent dermis and muscle, the splicing pattern remains identical with that seen in normal adult rat skin, with two of the three spliced segments (EIIIA and EIIIB) excluded from FN mRNA. In contrast, these two segments are included in the FN mRNA present in the cells at the base of the wound. As a result, the mRNA in this region is spliced in a pattern identical with that found during early embryogenesis. The finding that the pattern of FN splicing during wound healing resembles an embryonic pattern suggests that alternative splicing may be used during wound healing as a mechanism to generate forms of FN that may be functionally more appropriate for the cell migration and proliferation associated with tissue repair.

Animals↗
PubMed1989

Alternative splicing of fibronectin is temporally and spatially regulated in the chicken embryo.

The primary gene transcript for the adhesive extracellular matrix glycoprotein fibronectin (FN) is alternatively spliced in three regions (EIIIA, EIIIB and V). At least one of these regions (V) has been shown to encode cell-binding sites, suggesting that splicing represents a mechanism to create functionally different forms of FN at different times and places. In order to test this hypothesis, we have examined the extent of alternative splicing of fibronectin during embryonic development. The distribution of the different spliced forms of FN mRNA in developing chicken embryos was determined using probes specific for the spliced regions in ribonuclease protection and in situ hybridization experiments. At embryonic day 2-4 (E2-4), all three spliced regions were included wherever FN mRNA was detected. At E16, however, we found spatially distinct splicing differences within the embryo, with cell-type-specific splicing excluding EIIIA and/or EIIIB in some tissues. In contrast, we did not detect exclusion of the V region. In a more detailed developmental study of the simplest of these tissues, the chorioallantoic membrane, we found that EIIIB was preferentially excluded after the completion of growth. These results suggest that FN splicing is used during development as a mechanism to create different forms of FN within the extracellular matrix by the inclusion or exclusion of specific segments. The data are consistent with an essential role for one of these segments, EIIIB, in the migration and/or proliferation of embryonic cells prior to their terminal differentiation and also suggest possible roles for the EIIIA segment.

Allantois↗
PubMed1988

Evidence that migratory oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells are kept out of the rat retina by a barrier at the eye-end of the optic nerve.

There is evidence that oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells migrate along the developing rat optic nerve from the chiasm toward the eye before differentiating into oligodendrocytes that myelinate the retinal ganglion cell axons in the nerve. Why, then, do these progenitor cells not migrate into the eye, differentiate into oligodendrocytes and myelinate the nerve fibre layer of the retina? Myelination would opacify the neural retina and thereby severely impair vision. Here we provide evidence that there is a barrier at the eye-end of the rat optic nerve that prevents the migration of O-2A progenitor cells into the retina. Our findings in the rat support a previous hypothesis that such a barrier keeps myelin-forming glial cells out of the human retina.

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PubMed1988

Patterns of fibronectin gene expression and splicing during cell migration in chicken embryos.

A variety of evidence suggests that fibronectin (FN) promotes cell migration during embryogenesis, and it has been suggested that the deposition of FN along migratory pathways may also play a role in cell guidance. In order to investigate such a role for FN, it is important to determine the relative contribution of migrating and pathway-forming cells to the FN in the migratory track, as any synthesis of FN by the migrating cells might be expected to mask guidance cues provided by the exogenous FN from pathway-forming cells. We have therefore used in situ hybridization to determine in developing chicken embryos the distribution and alternative splicing of FN mRNA during three different cell migrations known to occur through FN-rich environments; neural crest cell migration, mesenchymal cell migration in the area vasculosa and endocardial cushion cell migration in the heart. Our results show that trunk neural crest cells do not contain significant FN mRNA during their initial migration. In contrast, migrating mesenchymal cells of the area vasculosa and endocardial cushion cells both contain abundant FN mRNA. Furthermore, the FN mRNA in these migrating mesenchymal and endocardial cells appears to be spliced in a manner identical with that present in the cells adjacent to their pathways. This in vivo evidence for FN synthesis by migrating and pathway cells argues against a generalized role for exogenously produced FN as a guidance mechanism for cell migration.

Animals↗
PubMed1987

Glial cells in the rat optic nerve and some thoughts on remyelination in the mammalian CNS.

Studies on the rat optic nerve in the past 5 years have produced two surprises. First, they demonstrated that there are two biochemically, developmentally and functionally distinct types of astrocytes in the optic nerve, and probably in white matter tracts throughout the CNS: one seems to be responsible for inducing endothelial cells to form the blood-brain barrier while the other seems to service nodes of Ranvier. Second, they showed that oligodendrocytes and type-2 astrocytes develop from a common bipotential (O-2A) progenitor cell that seems to migrate into the developing optic nerve, and may well migrate all over the CNS to wherever myelination is required; this implies that the neuroepithelial cells of the optic stalk are restricted to forming type-1 astrocytes. Some of the findings in the optic nerve may be relevant to the problem of CNS regeneration after injury. These include the following. (1) Reactive gliosis in white matter tracts seems to be mainly a function of type-1 astrocytes. (2) Proliferating O-2A progenitor cells are present in the adult CNS, raising the possibility that they may be able to produce new oligodendrocytes and type-2 astrocytes following injury and thereby aid regeneration. (3) Type-1 astrocytes seem to be able to respond to environmental signals and form localized barriers that block the migration of O-2A progenitor cells; it is conceivable that the same barriers block the migration of regenerating axonal growth cones.

Animals↗
PubMed1986

Molecular specialization of astrocyte processes at nodes of Ranvier in rat optic nerve.

The HNK-1 and L2 monoclonal antibodies are thought to recognize identical or closely associated carbohydrate epitopes on a family of neural plasma membrane glycoproteins, including myelin-associated glycoprotein, the neural cell adhesion molecule, and the L1 and J1 glycoproteins, all of which have been postulated to play a part in mediating cell-cell interactions in the nervous system. We have used these two antibodies in immunofluorescence and immunogold-electron microscopic studies of semithin and ultrathin frozen sections of adult rat optic nerve, respectively, and we show that they bind mainly to astrocyte processes around nodes of Ranvier. Most other elements of the nerve, including astrocyte cell bodies and large astrocytic processes, are not labeled by the antibodies. To our knowledge, this is the first demonstration that perinodal astrocyte processes are biochemically specialized. We provide evidence that one of the HNK-1+/L2+ molecules concentrated around perinodal astrocyte processes is the J1 glycoprotein; our findings, taken together with previously reported observations, suggest that the other known HNK-1+/L2+ molecules are not concentrated on these processes. Since anti-J1 antibodies previously have been shown to inhibit neuron to astrocyte adhesion in vitro, we hypothesize that J1 may play an important part in the axon-glial interactions that presumably are involved in the assembly and/or maintenance of nodes of Ranvier.

Animals↗
PubMed1986

Is reactive gliosis a property of a distinct subpopulation of astrocytes?

We have shown previously that the A2B5 monoclonal antibody distinguishes two types of glial fibrillary acidic protein-containing astrocytes in semithin frozen sections of adult rat optic nerve: A2B5- (type-1) astrocytes are found mainly at the periphery of the nerve, where they form the glial limiting membrane, while A2B5+ (type-2) astrocytes are found mainly in the interior of the nerve and constitute more than 65% of the astrocytes in the adult optic nerve. In the present study we show that although most astrocytes in semithin frozen sections of adult rat corpus callosum and optic nerve are A2B5+, the great majority of reactive astrocytes in similar sections of corpus callosum examined 20 weeks after a stab lesion, and in optic nerve examined 20 weeks after adult transection, are A2B5-. Although both A2B5+ and A2B5- astrocytes are stimulated to synthesize DNA in the first week after transection, adult optic nerves examined 20 weeks after transection contain only half as many astrocytes as do normal optic nerves: While A2B5+ astrocytes are reduced almost 10-fold, A2B5- astrocytes are increased by about 25%. We consider the simplest interpretation of these findings to be that type-1 astrocytes are largely responsible for forming glial scars in adult white matter following either a stab lesion or Wallerian degeneration and that in transected optic nerves, most type-2 astrocytes eventually die, possibly because they depend on axons for their long-term survival.

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PubMedDate not supplied

Proliferating bipotential glial progenitor cells in adult rat optic nerve.

We have shown previously that the rat optic nerve contains three types of macroglial cells--oligodendrocytes and two types of astrocytes--which develop as two distinct lineages. Type-1 astrocytes develop from one type of precursor cell beginning at embryonic day 16 (E16), while oligodendrocytes and then type-2 astrocytes develop from a common, bipotential progenitor cell beginning at birth (E21) and postnatal days 7-10 (P7-10), respectively. Here we report that proliferating bipotential oligodendrocyte-type-2 astrocyte (0-2A) progenitor cells are present in the adult rat optic nerve, raising the possibility that these cells are produced continually from self-renewing stem cells throughout life.

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PubMedDate not supplied

The oligodendrocyte-type-2 astrocyte cell lineage is specialized for myelination.

Astrocytes are one of the most numerous cell types in the vertebrate central nervous system (CNS) and yet their functions are largely unknown. In the rat optic nerve there are two distinct types of astrocyte: type-1 astrocytes develop from one type of precursor cell, and type-2 astrocytes develop from bipotential, oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells, that initially give rise to oligodendrocytes (which make myelin in the CNS), and then to type-2 astrocytes. Type-1 astrocytes form the glial limiting membrane at the periphery of the optic nerve and are probably responsible for glial scar formation following nerve transection. The functions of type-2 astrocytes, which, like oligodendrocytes, are found mainly in tracts of myelinated axons throughout the CNS, are unknown. In this report we provide evidence that processes from type-2 astrocytes contribute to the structure of nodes of Ranvier, suggesting that the O-2A cell lineage is specialized for constructing myelin sheaths and nodes in the mammalian CNS.

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