A role for HGF/SF in neural induction and its expression in Hensen's node during gastrulation

Development ◽  
1995 ◽  
Vol 121 (3) ◽  
pp. 813-824 ◽  
Author(s):  
A. Streit ◽  
C.D. Stern ◽  
C. Thery ◽  
G.W. Ireland ◽  
S. Aparicio ◽  
...  
Keyword(s):  
Neural Induction ◽  
Primitive Streak ◽  
Neural Plate ◽  
Neuronal Morphology ◽  
Collagen Gels ◽  
Scatter Factor ◽  
Neuronal Markers ◽  
Hepatocyte Growth ◽  
Overnight Culture

It was previously shown (Roberts, C., Platt, N., Streit, A., Schachner, M. and Stern, C. D. (1991) Development 112, 959–970) that grafts of Hensen's node into chick embryos enhanced and maintain expression of the L5 carbohydrate in neighbouring epiblast cells, and that antibodies against L5 inhibit neural induction by such a graft. We now show that L5 is initially widely expressed in the epiblast, but as neural induction proceeds it gradually becomes confined to and up-regulated in the early neural plate. L5 can therefore be considered as a marker for cells that are competent to respond to neural induction. We also show that Hepatocyte Growth Factor/Scatter Factor (HGF/SF) promotes the expression of L5 by extraembryonic epiblast in collagen gels after overnight culture. Explants cultured for several days in the presence of HGF/SF, as well as explants of prospective neural plate, can differentiate into cells with neuronal morphology expressing neuronal markers. To investigate whether HGF/SF is expressed in the chick embryo at appropriate stages of development, we produced specific cDNA probes and used them for in situ hybridization. We find that at the primitive streak stage, HGF/SF is expressed specifically in Hensen's node. We therefore propose that HGF/SF plays a role during the early steps of neural induction, perhaps by inducing or maintaining the competence of the epiblast to respond to neural inducing signals.

The spatial and temporal dynamics of Sax1 (CHox3) homeobox gene expression in the chick's spinal cord

Development ◽  
1994 ◽  
Vol 120 (7) ◽  
pp. 1817-1828 ◽  
Author(s):  
P. Spann ◽  
M. Ginsburg ◽  
Z. Rangini ◽  
A. Fainsod ◽  
H. Eyal-Giladi ◽  
...  
Keyword(s):  
Temporal Dynamics ◽  
Homeobox Gene ◽  
Primitive Streak ◽  
Neural Plate ◽  
Transverse Plane ◽  
Posterior Border ◽  
Anterior Border ◽  
Spatial And Temporal Dynamics ◽  
Specific Localization

Sax1 (previously CHox3) is a chicken homeobox gene belonging to the same homeobox gene family as the Drosophila NK1 and the honeybee HHO genes. Sax1 transcripts are present from stage 2 H&H until at least 5 days of embryonic development. However, specific localization of Sax1 transcripts could not be detected by in situ hybridization prior to stage 8-, when Sax1 transcripts are specifically localized in the neural plate, posterior to the hindbrain. From stages 8- to 15 H&H, Sax1 continues to be expressed only in the spinal part of the neural plate. The anterior border of Sax1 expression was found to be always in the transverse plane separating the youngest somite from the yet unsegmented mesodermal plate and to regress with similar dynamics to that of the segregation of the somites from the mesodermal plate. The posterior border of Sax1 expression coincides with the posterior end of the neural plate. In order to study a possible regulation of Sax1 expression by its neighboring tissues, several embryonic manipulation experiments were performed. These manipulations included: removal of somites, mesodermal plate or notochord and transplantation of a young ectopic notochord in the vicinity of the neural plate or transplantation of neural plate sections into the extraembryonic area. The results of these experiments revealed that the induction of the neural plate by the mesoderm has already occurred in full primitive streak embryos, after which Sax1 is autonomously regulated within the spinal part of the neural plate.

Chordin regulates primitive streak development and the stability of induced neural cells, but is not sufficient for neural induction in the chick embryo

Development ◽  
1998 ◽  
Vol 125 (3) ◽  
pp. 507-519 ◽  
Author(s):  
A. Streit ◽  
K.J. Lee ◽  
I. Woo ◽  
C. Roberts ◽  
T.M. Jessell ◽  
...  
Keyword(s):  
Neural Induction ◽  
Neural Tissue ◽  
Primitive Streak ◽  
Neural Plate ◽  
Neural Cells ◽  
Morphogenetic Protein ◽  
Neural Markers ◽  
Bmp Signalling ◽  
The Stability ◽  
Area Pellucida

We have investigated the role of Bone Morphogenetic Protein 4 (BMP-4) and a BMP antagonist, chordin, in primitive streak formation and neural induction in amniote embryos. We show that both BMP-4 and chordin are expressed before primitive streak formation, and that BMP-4 expression is downregulated as the streak starts to form. When BMP-4 is misexpressed in the posterior area pellucida, primitive streak formation is inhibited. Misexpression of BMP-4 also arrests further development of Hensen's node and axial structures. In contrast, misexpression of chordin in the anterior area pellucida generates an ectopic primitive streak that expresses mesoderm and organizer markers. We also provide evidence that chordin is not sufficient to induce neural tissue in the chick. Misexpression of chordin in regions outside the future neural plate does not induce the early neural markers L5, Sox-3 or Sox-2. Furthermore, neither BMP-4 nor BMP-7 interfere with neural induction when misexpressed in the presumptive neural plate before or after primitive streak formation. However, chordin can stabilise the expression of early neural markers in cells that have already received neural inducing signals. These results suggest that the regulation of BMP signalling by chordin plays a role in primitive streak formation and that chordin is not sufficient to induce neural tissue.

Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction

Development ◽  
1987 ◽  
Vol 99 (3) ◽  
pp. 311-325 ◽  
Author(s):  
C.R. Kintner ◽  
D.A. Melton
Keyword(s):  
Neural Development ◽  
Transcriptional Activation ◽  
Neural Induction ◽  
Early Response ◽  
Neural Plate ◽  
Cdna Clones ◽  
Epidermal Tissue ◽  
Early Expression ◽  
Neural Ectoderm

We have isolated Xenopus laevis N-CAM cDNA clones and used these to study the expression of N-CAM RNA during neural induction. The results show that the first marked increase in N-CAM RNA levels occurs during gastrulation when mesoderm comes in contact with ectoderm and induces neural development. In situ hybridization results show that the early expression of N-CAM RNA is localized to the neural plate and its later expression is confined to the neural tube. Induction experiments with explanted germ layers show that N-CAM RNA is not expressed in ectoderm unless there is contact with inducing tissue. Together these results suggest an approach to studying how ectoderm is committed to form neural rather than epidermal tissue. Specifically, the data suggest that neural commitment is marked and perhaps mediated by the transcriptional activation of genes, like N-CAM, in the neural ectoderm.

Timing and cell interactions underlying neural induction in the chick embryo

Development ◽  
1999 ◽  
Vol 126 (11) ◽  
pp. 2505-2514
Author(s):  
D.K. Darnell ◽  
M.R. Stark ◽  
G.C. Schoenwolf
Keyword(s):  
Neural Induction ◽  
Primitive Streak ◽  
Model System ◽  
Neural Plate ◽  
Neural Specification ◽  
Organizer Activity ◽  
Plate Morphology ◽  
Improved Model ◽  
Differentiation Event ◽  
Early Gastrula

Previous studies on neural induction have identified regionally localized inducing activities, signaling molecules, potential competence factors and various other features of this important, early differentiation event. In this paper, we have developed an improved model system for analyzing neural induction and patterning using transverse blastoderm isolates obtained from gastrulating chick embryos. We use this model to establish the timing of neural specification and the spatial distribution of perinodal cells having organizer activity. We show that a tissue that acts either as an organizer or as an inducer of an organizer is spatially co-localized with the prospective neuroectoderm immediately rostral to the primitive streak in the early gastrula. As the primitive streak elongates, this tissue with organizing activity and the prospective neuroectoderm rostral to the streak separate. Furthermore, we show that up to and through the mid-primitive streak stage (i.e., stage 3c/3+), the prospective neuroectoderm cannot self-differentiate (i.e., express neural markers and acquire neural plate morphology) in isolation from tissue with organizer activity. Signals from the organizer and from other more caudal regions of the primitive streak act on the rostral prospective neuroectoderm and the latter gains potency (i.e., is specified) by the fully elongated primitive streak stage (i.e., stage 3d). Transverse blastoderm isolates containing non-specified, prospective neuroectoderm provide an improved model system for analyzing early signaling events involved in neuraxis initiation and patterning.

Modulation of scatter factor/hepatocyte growth factor activity by cell-substratum adhesion

1994 ◽  
Vol 107 (5) ◽  
pp. 1265-1275 ◽  
Author(s):  
P. Clark
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Separation ◽  
Prolonged Exposure ◽  
Collagen Gels ◽  
Scatter Factor ◽  
Tubule Formation ◽  
Hepatocyte Growth ◽  
Cell Cell

Scatter factor/hepatocyte growth factor (SF/HGF) is a multifunctional growth and motility factor whose activities vary with cell type. Here, the composition of the substratum was found to profoundly alter the scattering activities of SF/HGF, but not its mitogenetic effects, in MDCK cells. Whereas enhancement of DNA synthesis and induction of cell flattening by SF/HGF were independent of substratum composition (i.e. occurred on both fibronectin and vitronectin surfaces), colony dispersion as a result of cell separation fails to occur or is markedly reduced on surfaces where vitronectin is the major adhesive ligand. Prolonged exposure of non-scattering cultures to SF/HGF resulted in cells at colony margins producing long protrusions, which indicate that the motility of these cells is stimulated but ‘frustrated’ by the lack of breakdown of cell-cell adhesion. Scattering therefore appears to comprise two major components: increased motility and breakdown of cell-cell adhesion. The pathway leading to the breakdown of cell-cell contacts is modulated by downstream signals from extracellular matrix receptors. When cultured on immobilised fibronectin, vitronectin or a surface containing both, colony dissociation correlates with the presence of fibronectin, suggesting that positive signals from fibronectin receptors are required for SF/HGF-induced cell separation. Comparison of the findings in this study with those of a recent report on the modulation of SF/HGF-induced tubulogenesis by ECM (Santos, O. F. P. and Nigam, S. K. (1993) Dev. Biol. 160, 293–302), where vitronectin in type-1 collagen gels alters the pattern of SF/HGF-induced MDCK tubule formation from highly branched to long and unbranched, suggests that cell motility enhancement leads to tubule formation whereas the breakdown of cell-cell adhesion is required for tubule branching.

Hepatocyte growth factor/scatter factor and its receptor c-met: localisation and expression in the human placenta throughout pregnancy

1996 ◽  
Vol 151 (3) ◽  
pp. 459-467 ◽  
Author(s):  
D E Clark ◽  
S K Smith ◽  
A M Sharkey ◽  
H M Sowter ◽  
D S Charnock-Jones
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Human Placenta ◽  
Extravillous Trophoblast ◽  
Human Embryos ◽  
Rt Pcr ◽  
Placental Development ◽  
Scatter Factor ◽  
Hepatocyte Growth

Abstract Hepatocyte growth factor (HGF), also known as scatter factor, acts via the c-met receptor resulting in pronounced effects on certain epithelial cells. We hypothesised that HGF would be important in placental development where the trophoblast represents a specialised barrier of epithelial origin. In this paper we examine the expression and production of HGF and its receptor in the human placenta throughout pregnancy. In addition, RT-PCR was undertaken on human embryos to ascertain whether preimplantation embryonic or trophoblast cells were under the influence of this growth factor. In samples from the first trimester of pregnancy in situ hybridisation with a c-met antisense probe detected message expression in villous cytotrophoblast and in decidual glands but not in extravillous trophoblast. Some c-met expression was detected in cytotrophoblast from the second trimester placentae; this declined to negligible levels by term. Staining with an anti c-met antibody largely confirmed these findings but found relatively strong staining of cytotrophoblast at term. HGF was confined to the villous core throughout pregnancy when examined by both in situ hybridisation and immunohistochemistry. Trophoblast was consistently negative for HGF. Pre-implantation embryos examined by RT-PCR were negative for both c-met and HGF mRNA. These results indicate that the HGF may exert an important influence on cytotrophoblast throughout the process of placental formation and growth. Journal of Endocrinology (1996) 151, 459–467

Branching morphogenesis of human mammary epithelial cells in collagen gels

1994 ◽  
Vol 107 (12) ◽  
pp. 3557-3568 ◽  
Author(s):  
F. Berdichevsky ◽  
D. Alford ◽  
B. D'Souza ◽  
J. Taylor-Papadimitriou
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Mammary Epithelial Cells ◽  
Branching Morphogenesis ◽  
Mammary Epithelial ◽  
Collagen Gels ◽  
Scatter Factor ◽  
Human Mammary Epithelial ◽  
Hepatocyte Growth

To study the morphogenesis of human epithelial cells in vitro we have used a three-dimensional collagen matrix and a newly developed mammary epithelial cell line, 1–7 HB2. In standard medium 1–7 HB2 cells formed compact balls/spheres inside collagen type I gels, while cocultivation with various fibroblast cell lines or growth in fibroblast-conditioned media resulted in the appearance of branching structures. At least two different soluble factors secreted by fibroblasts were found to be implicated in the branching morphogenesis. Firstly, hepatocyte growth factor/scatter factor could induce branching in a concentration-dependent manner. Moreover, a polyclonal serum against hepatocyte growth factor/scatter factor completely inhibited the branching morphogenesis induced by medium conditioned by MRC-5 fibroblast cells. In contrast, a morphogenetic activity secreted by human foreskin fibroblasts was identified that appears to be different from hepatocyte growth factor/scatter factor and from a number of other well-characterized growth factors or cytokines. This model system has been used to examine the role of integrins in mammary morphogenesis. The expression of the alpha 2 beta 1, alpha 3 beta 1 and alpha 6 beta 4 integrins was decreased when cells were plated on collagen gels. The addition of specific blocking monoclonal antibodies directed to the alpha 2- and beta 1-integrin subunits to growth media impaired cell-cell interactions and interfered with the formation of compact structures inside collagen gels, suggesting that the alpha 2 beta 1 integrin can control intercellular adhesion in mammary morphogenesis. In contrast one of the blocking monoclonal antibodies against the alpha 3-integrin subunit (P1B5) mimicked the effect of soluble ‘morphogens’. Our results suggest that the modulation of alpha 3 beta 1 activity may represent an important event in the induction of branching morphogenesis of human mammary epithelial cells.

scholarly journals Initiation of Murine Embryonic Erythropoiesis: A Spatial Analysis

Blood ◽  
1997 ◽  
Vol 89 (4) ◽  
pp. 1154-1164 ◽  
Author(s):  
Louise Silver ◽  
James Palis
Keyword(s):  
Expression Patterns ◽  
Erythroid Differentiation ◽  
Primitive Streak ◽  
Neural Plate ◽  
Temporal Expression ◽  
Targeted Disruption ◽  
Mesoderm Cell ◽  
Temporal And Spatial ◽  
Extraembryonic Mesoderm

Abstract Hematopoiesis in the mouse conceptus begins in the visceral yolk (VYS), with primitive erythroblasts first evident in blood islands at the headfold stage (E8.0). VYS erythropoiesis is decreased or abrogated by targeted disruption of the hematopoietic transcription factors tal-1, rbtn2, GATA-1, and GATA-2. To better understand the potential roles of these genes, and to trace the initial temporal and spatial development of mammalian embryonic hematopoiesis, we examined their expression patterns, and that of βH1-globin, in normal mouse conceptuses by means of in situ hybridization. Attention was focused on the 36-hour period from mid-primitive streak to early somite stages (E7.25 to E8.5), when the conceptus undergoes rapid morphologic changes with formation of the yolk sac and blood islands. Each of these genes was expressed in extraembryonic mesoderm, from which blood islands are derived. This VYS expression occurred in a defined temporal sequence: tal-1 and rbtn2 transcripts were detected earlier than the others, followed by GATA-2 and GATA-1, and then by βH1-globin. Transcripts for all of these genes were present in VYS mesoderm cell masses at the neural plate stage (E7.5), indicating commitment of these cells to the erythroid lineage before the appearance of morphologically recognizable erythroblasts. By early somite stages (E8.5), GATA-2 mRNA expression is downregulated in VYS blood islands as terminal primitive erythroid differentiation proceeds. We conclude that primitive mammalian erythropoiesis arises during gastrulation through the ordered temporal expression of tal-1, rbtn2, GATA2, and GATA-1 in a subset of extraembryonic mesoderm cells. During the stages analyzed, tal-1 and rbtn2 expression was also present in posterior embryonic mesoderm, while GATA-1 and GATA-2 expression was evident in extraembryonic tissues of ectodermal origin.

scholarly journals Characterization of the Scatter Factor/Hepatocyte Growth Factor Gene Promoter

1995 ◽  
Vol 270 (2) ◽  
pp. 830-836 ◽  
Author(s):  
Antje Plaschke-Schlütter ◽  
Jürgen Behrens ◽  
Ermanno Gherardi ◽  
Walter Birchmeier
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Gene Promoter ◽  
Scatter Factor ◽  
Factor Gene ◽  
Growth Factor Gene ◽  
Hepatocyte Growth
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