Developmental expression of syndecan, an integral membrane proteoglycan, correlates with cell differentiation (original) (raw)
Related papers
Embryonic neurons adapt to the inhibitory proteoglycan aggrecan by increasing integrin expression
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1999
The primary mediators of cell migration during development, wound healing and metastasis, are receptors of the integrin family. In the developing and regenerating nervous system, chondroitin sulfate proteoglycans (CSPGs) inhibit the integrin-dependent migration of neuronal growth cones. Here we report that embryonic sensory neurons cultured on the growth-promoting molecule laminin in combination with the inhibitory CSPG aggrecan rapidly adapt to inhibition. Adaptation is associated with a two- to threefold increase in the levels of RNA and surface protein for two laminin receptors, integrin alpha6beta1 and alpha3beta1, indicating that integrin expression is regulated by aggrecan. Increased integrin expression is associated both with increases in neuronal cell adhesion/outgrowth and with decreases in the ability of aggrecan to inhibit cell adhesion. Directly increasing integrin expression by adenoviral infection is sufficient to eliminate the inhibitory effects of aggrecan, indicatin...
1995
Midkine (MK) and heparin binding-growth associated molecule (HB-GAM or pleiotrophin), constitute a new family of heparin-binding proteins implicated in the regulation of growth and differentiation (T. Muramatsu (1993) Int. J. Dev. Biol. 37, 183-188). We used affinity-purified antibodies against MK and HB-GAM to analyze their distribution during mouse embryonic development. From 9 to 14.5 day post-coitum (dpc), both proteins were detected in central and peripheral nervous systems, facial processes, limb buds, sense organs, respiratory, digestive, urogenital, and skeletal systems. MK and HB-GAM were often localized on the surface of differentiating cells and in basement membranes of organs undergoing epithelial-mesenchymal interactions. The levels of MK protein decreased considerably in the 16.5 dpc embryo, whereas HB-GAM staining persisted in many tissues. Our in situ hybridization results revealed a widespread expression of MK transcripts that was not always consistent with the distribution of MK protein in developing tissues. In many epithelio-mesenchy-mal organs MK and HB-GAM were codistributed with syndecan-1, a cell surface proteoglycan. In limb buds and facial processes, MK, HB-GAM, and syndecan-1 were localized to the apical epithelium and the adjacent proliferating mesenchyme. Both MK and HB-GAM bound syndecan-1 in solid-phase assays in a heparan sulfatedependent manner. The biological effects of MK and HB-GAM on limb and facial mesenchyme were studied in vitro by application of beads preloaded with the proteins. Neither MK nor HB-GAM stimulated mesenchymal cell proliferation or induced syndecan-1 expression. Taken together these results indicate that MK and HB-GAM may play regulatory roles in differentiation and morphogenesis of the vertebrate embryo, particularly in epitheliomesenchymal organs, and suggest molecular interactions with syndecan-1.
Mesenchymal-epithelial transition in development and reprogramming
E pithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) are fundamental evolutionarily conserved mechanisms employed at different stages of morphogenesis and organogenesis to generate the body plan of metazoans. EMT involves the progressive loss of epithelial cell polarity, downregulation of junctional complexes and reorganization of the actin cytoskeleton to confer the migratory phenotype necessary to execute the extensive cellular movements that will give rise to the germ layers and later to tissues 1. MET is employed to generate epithelia at different developmental stages. During MET, mesenchymal cells progressively establish api-cobasal polarity through an evolutionarily conserved group of proteins and distinct but well-defined mechanisms 2 : polarity-related cell-surface receptors generate different membrane domains and become stabilized with the assembly of junctional complexes, leading to the formation of tight junctions at the apex of the lateral domain and the organization of cytoskeletal structures and organ-elles 2. Evidence of embryonic cells displaying attributes of both epithelial and mesenchymal phenotypes supports the existence of transient intermediate EMT and MET stages 2-5 , a phenomenon that is also observed in carcinoma 1,6. Long germ-band insects, such as Drosophila, assemble the first epithelium through the migration of nuclei to the periphery of the egg followed by rapid cellularization 7,8. The newly formed epithelial blas-toderm will engage in complex morphogenetic movements to elongate the embryo and simultaneously create invagination sites by the localized formation of a contractile actomyosin ring in cells within the body cavity. This process initiates gastrulation at distinct sites along the body axis 7. Endodermal cells forming the anterior and posterior proctodaeal invaginations engage in an EMT-MET sequence and merge to give rise to the midgut. By contrast, ectodermal cells that form the foregut and the hindgut will retain their epithelial phenotype 7,8. An EMT-MET cycle is also observed for mesodermal cells that invaginate through the ventral furrow to form the dorsal vessel gonadal sheet and the Malpighian tubules 9. Most other meta-zoan development proceeds through a series of cleavages of the fertilized egg and the progressive assembly of epithelial-like structures. These embryos engage in gastrulation by activating epithelial plasticity programmes, including EMT, as soon as the blastocoelic cavity is formed 10. Although morphogenetic movements are quite diverse in different species, they adhere to a set of general principles of epithelial cell plasticity, reviewed in detail elsewhere 11. Embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) undergo EMT and MET to differentiate into somatic cell types. Similarly, differentiated somatic cells can be reprogrammed into pluripotent cells by a sequential EMT-MET, with MET being a critical step for the acquisition of pluripotency 12. In addition to the establishment of epithelial polarity, MET in reprogramming is associated with metabolic switching, epigenetic modifications and cell fate changes 13 , providing a unique opportunity to investigate the relationships between these cellular events. Although morphogenesis and setting the body plan require cell plasticity and EMT-MET cycles, later postnatal development requires stabilization of epithelial tissues. EMT-associated transcription factors are rarely detectable in adult epithelial tissues 14 and several factors were recently shown to protect this epithelial state. For instance, inactivation of the Ets superfamily transcription factor ELF5 induces EMT in the normal mammary gland, affecting alveo-logenesis and increasing the number of mammary stem cells 15. In vitro, ELF5 overexpression prevents transforming growth factor-β (TGF-β)-induced EMT in normal murine mammary cells and can partially revert the mesenchymal phenotype of breast adenocar-cinoma cells 15. Grainyhead-like 2 (GRHL2), a DNA-binding protein that maintains the non-neural ectodermal epithelium 16 , binds to CDH1 (which encodes E-cadherin) intron 2 and the promoter of CLDN4 (which encodes claudin-4) to augment their transcription 17,18. As a result, GRHL2 suppression induces a mesenchymal-like phenotype in ovarian epithelial carcinoma cell lines. Finally, the Ovol1 and Ovol2 transcription factors maintain epithelial integrity in the embryonic epidermis 19 and Ovol2 also in the mam-mary gland 20 , by repressing EMT-associated transcription factors. One such factor, Zeb1, is controlled by a regulatory loop involving repression directly by GRHL2 and Ovol2 or indirectly through microRNA-200 (ref. 18). This Review focuses on the mechanisms that drive the induction and maintenance of epithelial tissues in development, the molecular drivers that contribute to epithelial cell polarization and the role of MET in reprogramming. During organogenesis, epithelial cells can give rise to mesenchymal cells through epithelial-mesenchymal transition. The reverse process, mesenchymal-epithelial transition (MET), can similarly generate epithelial cells. Transitions between epi-thelial and mesenchymal states are also critical for the induction of pluripotent stem cells from somatic cells. This Review discusses the relatively less characterized process of MET, focusing on the genesis of apicobasal cell polarity and exploring the roles of MET in development and reprogramming.
Basal lamina heparan sulphate proteoglycan is involved in otic placode invagination in chick embryos
Anatomy and Embryology, 2000
Formation of the otocyst from the otic placode appears to differ from invagination of other cup-shaped organ primordia. It is known that the cellular cytoskeleton plays a limited role in otic placode invagination, whilst the extracellular matrix underlying the otic primordium intervenes in the folding process. In this study we have analysed the role of the basal lamina heparan sulphate proteoglycan in otic primordium invagination. At 10 H.H. stage, heparan sulphate proteoglycan immunomarking begins to appear on the otic placode basal lamina, increasing noticeably at 13 H.H. stage, coinciding with maximum folding of the otic epithelium, and is still present at later stages. Enzyme degradation of heparan sulphate proteoglycan in the otic primordium basal lamina, by means of microinjection with heparinase III prior to folding, significantly disrupts invagination of the otic placode, which remains practically flat, with a significant reduction in the depth of the otic pit and an increase in the diameter of the otic opening. The immunocytochemistry analysis revealed a notable depletion of basal lamina heparan sulphate proteoglycan in the otic primordia microinjected with heparinase, with no statistically significant differences observed in the volume or rate of cell proliferation in the otic epithelium relative to the control, which suggests that heparan sulphate proteoglycan disruption does not interfere with the epithelial growth. In addition, a study of apoptosis distribution by the TUNEL method confirmed that treatment with heparinase does not cause interference with cell survival in the otic epithelium. Our findings support the theory that otic primordium invagination may be regulated, at least in part, by the basal lamina components, which might contribute towards anchoring the otic epithelium to adjacent structures.
International Journal of Developmental Neuroscience, 2000
There is increasing evidence that proteoglycans, particularly chondroitin sulfate proteoglycans (CSPGs), are integral components in the assembly of the extracellular matrix during early stages of histogenesis. The dierential expression of several CSPGs in the developing CNS has raised questions on their origin, phenotype (chemical and structural characteristics), regulation of expression and function. The S103L monoclonal antibody has been an invaluable speci®c reagent to identify and study a large and abundant CSPG in embryonic chick brain. In the present study we demonstrate that during embryogenesis of the chick CNS, the S103L CSPG (B-aggrecan) is synthesized by neurons of all major neuronal cell types but not by astrocytes, is developmentally regulated, and is associated predominantly with neuronal somata, suggesting that neuronal-speci®c regulatory mechanisms control the expression of the S103L CSPG in culture. Neurons also exhibit dierential expression of glycosaminoglycan type (i.e., KS) and sulfation patterns on dierent CSPGs when compared to astrocytes, meningial cells or chondrocytes, implying the existence of additional, cell type-speci®c modes of regulation of the ®nal CSPG phenotype (chemical and structural posttranslational characteristics). A speci®c temporal pattern of expression of the S103L-CSPG was observed which may contribute to conditions that induce or stabilize speci®c cell phenotypes during CNS development. In contrast, the other major CSPG in the CNS recognized by the HNK-1 antibody, is synthesized by all cell types of dierent cell lineages over the entire embryonic period, suggesting a more global cell maintenance function for this CSPG. 7
Development, 1991
In this study, we describe the distribution of various classes of proteoglycans and their potential matrix ligand, hyaluronan, during neural crest development in the trunk region of the chicken embryo. Different types of chondroitin and keratan sulfate proteoglycans were recognized using a panel of monoclonal antibodies produced against specific epitopes on their glycosaminoglycan chains. A heparan sulfate proteoglycan was identified by an antibody against its core protein. The distribution of hyaluronan was mapped using a biotinylated fragment that corresponds to the hyaluronanbinding region of cartilage proteoglycans. Four major patterns of proteoglycan immunoreactivity were observed. (1) Chondroitin-6-sulfate-rich proteoglycans and certain keratan sulfate proteoglycans were absent from regions containing migrating neural crest cells, but were present in interstitial matrices and basement membranes along prospective migratory pathways such as the ventral portion of the sclerotome. Although initially distributed uniformly along the rostrocaudal extent of the sclerotome, these proteoglycans became rearranged to the caudal portion of the sclerotome with progressive migration of neural crest cells through the rostral sclerotome and their aggregation into peripheral ganglia. (2) A subset of chondroitin/keratan sulfate proteoglycans bearing primarily unsulfated chondroitin chains was observed exclusively in regions where neural crest cells were absent or delayed from entering, such as the perinotochordal and subepidermal spaces. (3) A subset of chondroitin/keratan sulfate proteoglycans was restricted to the perinotochordal region and, following gangliogenesis, was arranged in a metameric pattern corresponding to the sites where presumptive vertebral arches form. (4) Certain keratan sulfate proteoglycans and a heparan sulfate proteoglycan were observed in basement membranes and in an interstitial matrix uniformly distributed along the rostrocaudal extent of the sclerotome. After gangliogenesis, the neural crestderived dorsal root and sympathetic ganglia contained both these proteoglycan types, but were essentially free of other chondroitin/keratan-proteoglycan subsets. Hyaluronan generally colocalized with the first set of proteoglycans, but also was concentrated around migrating neural crest cells and was reduced in neural crest-derived ganglia. These observations demonstrate that proteoglycans have diverse and dynamic distributions during times of neural crest development and chondrogenesis of the presumptive vertebrae. In general, chondroitin/keratan sulfate proteoglycans are abundant in regions where neural crest cells are absent, and their segmental distribution inversely correlates with that of neural crest-derived ganglia.
Development (Cambridge, England), 1991
Syndecan is an integral membrane proteoglycan that binds cells to several interstitial extracellular matrix components and binds to basic fibroblast-growth factor (bFGF) thus promoting bFGF association with its high-affinity receptor. We find that syndecan expression undergoes striking spatial and temporal changes during the period from the early cleavage through the late gastrula stages in the mouse embryo. Syndecan is detected initially at the 4-cell stage. Between the 4-cell and late morula stages, syndecan is present intracellularly and on the external surfaces of the blastomeres but is absent from regions of cell-cell contact. At the blastocyst stage, syndecan is first detected at cell-cell boundaries throughout the embryo and then, at the time of endoderm segregation, becomes restricted to the first site of matrix accumulation within the embryo, the interface between the primitive ectoderm and primitive endoderm. During gastrulation, syndecan is distributed uniformly on the ba...