Expression of syndecan, a putative low affinity fibroblast growth factor receptor, in the early mouse embryo

Development ◽  
1991 ◽  
Vol 113 (1) ◽  
pp. 339-351 ◽  
Author(s):  
A.E. Sutherland ◽  
R.D. Sanderson ◽  
M. Mayes ◽  
M. Seibert ◽  
P.G. Calarco ◽  
...  

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 basolateral cell surfaces of the embryonic ectoderm and definitive embryonic endoderm, but is expressed with an anteroposterior asymmetry on the surface of embryonic mesoderm cells, suggesting that it contributes to the process of mesoderm specification. In the extraembryonic region, syndecan is not detectable on most cells of the central core of the ectoplacental cone, but is strongly expressed by cells undergoing trophoblast giant cell differentiation and remains prominent on differentiated giant cells, suggesting a role in placental development. Immunoprecipitation studies indicate that the size of the syndecan core protein, although larger than that found in adult tissues (75 versus 69 × 10(3) Mr), does not change during peri-implantation development. The size distribution of the intact proteoglycan does change, however, indicating developmental alterations in its glycosaminoglycan composition. These results indicate potential roles for syndecan in epithelial organization of the embryonic ectoderm, in differential axial patterning of the embryonic mesoderm and in trophoblast giant cell function.

2018 ◽  
Author(s):  
Thao Nguyen ◽  
Laurence Duchesne ◽  
Gautham Hari Narayana Sankara Narayana ◽  
Nicole Boggetto ◽  
David D. Fernig ◽  
...  

AbstractN-cadherin adhesion has been reported to enhance cancer and neuronal cell migration either by mediating actomyosin-based force transduction or initiating Fibroblast Growth Factor Receptor (FGFR)-dependent biochemical signalling. Here we show that FGFR1 reduces N-cadherin-mediated cell migration. Both proteins are co-stabilised at cell-cell contacts through direct interaction. As a consequence, cell adhesion is strengthened, limiting the migration of cells on N-cadherin. Both the inhibition of migration and the stabilisation of cell adhesions require the FGFR activity stimulated by N-cadherin engagement. FGFR1 stabilises N-cadherin at the cell membrane through a pathway involving Src and p120. Moreover, FGFR1 stimulates the anchoring of N-cadherin to actin. We found that the migratory behaviour of cells depends on an optimum balance between FGFR-regulated N-cadherin adhesion and actin dynamics. Based on these findings we propose a positive feedback loop between N-cadherin and FGFR at adhesion sites limiting N-cadherin-based single cell migration.


Oncogene ◽  
2019 ◽  
Vol 38 (35) ◽  
pp. 6283-6300 ◽  
Author(s):  
Thao Nguyen ◽  
Laurence Duchesne ◽  
Gautham Hari Narayana Sankara Narayana ◽  
Nicole Boggetto ◽  
David D. Fernig ◽  
...  

2001 ◽  
Vol 154 (4) ◽  
pp. 841-856 ◽  
Author(s):  
Lihsia Chen ◽  
Bryan Ong ◽  
Vann Bennett

This study shows that L1-like adhesion (LAD-1), the sole Caenorhabditis elegans homologue of the L1 family of neuronal adhesion molecules, is required for proper development of the germline and the early embryo and embryonic and gonadal morphogenesis. In addition, the ubiquitously expressed LAD-1, which binds to ankyrin-G, colocalizes with the C. elegans ankyrin, UNC-44, in multiple tissues at sites of cell–cell contact. Finally, we show that LAD-1 is phosphorylated in a fibroblast growth factor receptor (FGFR) pathway-dependent manner on a tyrosine residue in the highly conserved ankyrin-binding motif, FIGQY, which was shown previously to abolish the L1 family of cell adhesion molecule (L1CAM) binding to ankyrin in cultured cells. Immunofluorescence studies revealed that FIGQY-tyrosine–phosphorylated LAD-1 does not colocalize with nonphosphorylated LAD-1 or UNC-44 ankyrin but instead is localized to sites that undergo mechanical stress in polarized epithelia and axon–body wall muscle junctions. These findings suggest a novel ankyrin-independent role for LAD-1 related to FGFR signaling. Taken together, these results indicate that L1CAMs constitute a family of ubiquitous adhesion molecules, which participate in tissue morphogenesis and maintaining tissue integrity in metazoans.


1998 ◽  
Vol 9 (8) ◽  
pp. 2269-2285 ◽  
Author(s):  
John Moffett ◽  
Erica Kratz ◽  
Jason Myers ◽  
Ewa K. Stachowiak ◽  
Robert Z. Florkiewicz ◽  
...  

Induction of the fibroblast growth factor-2 (FGF-2) gene and the consequent accumulation of FGF-2 in the nucleus are operative events in mitotic activation and hypertrophy of human astrocytes. In the brain, these events are associated with cellular degeneration and may reflect release of the FGF-2 gene from cell contact inhibition. We used cultures of human astrocytes to examine whether expression of FGF-2 is also controlled by soluble growth factors. Treatment of subconfluent astrocytes with interleukin-1β, epidermal or platelet-derived growth factors, 18-kDa FGF-2, or serum or direct stimulation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate or adenylate cyclase with forskolin increased the levels of 18-, 22-, and 24-kDa FGF-2 isoforms and FGF-2 mRNA. Transfection of FGF-2 promoter–luciferase constructs identified a unique −555/−513 bp growth factor-responsive element (GFRE) that confers high basal promoter activity and activation by growth factors to a downstream promoter region. It also identified a separate region (−624/−556 bp) essential for PKC and cAMP stimulation. DNA–protein binding assays indicated that novel cis-acting elements and trans-acting factors mediate activation of the FGF-2 gene. Southwestern analysis identified 40-, 50-, 60-, and 100-kDa GFRE-binding proteins and 165-, 112-, and 90-kDa proteins that interacted with the PKC/cAMP-responsive region. The GFRE and the element essential for PKC and cAMP stimulation overlap with the region that mediates cell contact inhibition of the FGF-2 promoter. The results show a two-stage regulation of the FGF-2 gene: 1) an initial induction by reduced cell contact, and 2) further activation by growth factors or the PKC-signaling pathway. The hierarchic regulation of the FGF-2 gene promoter by cell density and growth factors or PKC reflects a two-stage activation of protein binding to the GFRE and to the PKC/cAMP-responsive region, respectively.


Blood ◽  
2001 ◽  
Vol 97 (11) ◽  
pp. 3450-3457 ◽  
Author(s):  
Iain R. Asplin ◽  
Sean M. Wu ◽  
Smitha Mathew ◽  
Gourab Bhattacharjee ◽  
Salvatore V. Pizzo

The fibroblast growth factor (FGF) family has an important role in processes such as angiogenesis, wound healing, and development in which precise control of proteinase activity is important. The human plasma proteinase inhibitor α2-macroglobulin (α2M) regulates cellular growth by binding and modulating the activity of many cytokines and growth factors. These studies investigate the ability of native and activated α2M (α2M*) to bind to members of the FGF family. Both α2M and α2M* bind specifically and saturably to FGF-1, -2, -4, and -6, although the binding to α2M* is of significantly higher affinity. Neither α2M nor α2M* bind to FGF-5, -7, -9, or -10. FGF-2 was chosen for more extensive study in view of its important role in angiogenesis. It was demonstrated that FGF-2 binds to the previously identified TGF-β binding site. The α2M* inhibits FGF-2–dependent fetal bovine heart endothelial cell proliferation in a dose-dependent manner. Unexpectedly, α2M* does not affect FGF-2–induced vascular tubule formation on Matrigel basement membrane matrix or collagen gels. Further studies demonstrate that FGF-2 partitions between fluid-phase α2M* and solid-phase Matrigel or collagen. These studies suggest that the ability of α2M* to modulate the activity of FGF-2 is dependent on an interplay with extracellular matrix components.


Development ◽  
1978 ◽  
Vol 48 (1) ◽  
pp. 239-247
Author(s):  
J. Rossant ◽  
R. L. Gardner ◽  
H. L. Alexandre

Chimaeric conceptuses have been produced by injection of 5½- and 6½-day extra-embryonic ectoderm and 5½-day embryonic and extra-embryonic endoderm into 3½-day mouse blastocysts. Extra-embryonic ectoderm cells contributed only to the ectoplacental cone and/or trophoblast giant cell fractions, reflecting the probable trophectoderm origin of these cells. Proximal (visceral) endoderm cells overlying both the embryonic and extra-embryonic ectoderm contributed cells only to the endoderm of the visceral yolk sac, indicating that the definitive embryonic endoderm has not formed by 5½ days p.c.


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