scholarly journals Characterisation of the transcriptional dynamics underpinning the function, fate, and migration of the mouse Anterior Visceral Endoderm

2021 ◽  
Author(s):  
Shifaan Thowfeequ ◽  
Jonathan Fiorentino ◽  
Di Hu ◽  
Maria Solovey ◽  
Sharon Ruane ◽  
...  
Keyword(s):  
Primitive Streak ◽  
Pharmacological Intervention ◽  
Visceral Endoderm ◽  
Migratory Behaviour ◽  
Tight Coupling ◽  
Transient Nature ◽  
Transcriptional Dynamics ◽  
And Migration ◽  
And Function ◽  
Anterior Visceral Endoderm

During early post-implantation development of the mouse embryo, the Anterior Visceral Endoderm (AVE) differs from surrounding visceral endoderm (VE) in its migratory behaviour and ability to restrict primitive streak formation to the opposite side of the egg cylinder. In order to characterise the molecular basis for the unique properties of the AVE, we combined single-cell RNA-sequencing of the VE prior to and during AVE migration, with high-resolution imaging, short-term lineage labelling, phosphoproteomics and pharmacological intervention. This revealed the transient nature of the AVE, the emergence of heterogeneities in AVE transcriptional states relative to position of cells, and its prominence in establishing gene expression asymmetries within the spatial constraints of the embryo. We identified a previously unknown requirement of Ephrin- and Semaphorin-signalling for AVE migration. These findings point to a tight coupling of transcriptional state and position in the AVE and reveal molecular heterogeneities underpinning its migratory behaviour and function.

scholarly journals Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e17620 ◽  
Author(s):  
Daniel W. Stuckey ◽  
Aida Di Gregorio ◽  
Melanie Clements ◽  
Tristan A. Rodriguez
Keyword(s):  
Primitive Streak ◽  
Visceral Endoderm ◽  
Anterior Visceral Endoderm

HNF3beta and Lim1 interact in the visceral endoderm to regulate primitive streak formation and anterior-posterior polarity in the mouse embryo

Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4499-4511 ◽  
Author(s):  
A. Perea-Gomez ◽  
W. Shawlot ◽  
H. Sasaki ◽  
R.R. Behringer ◽  
S. Ang
Keyword(s):  
Mouse Embryo ◽  
Primitive Streak ◽  
Axis Formation ◽  
Visceral Endoderm ◽  
Primary Defect ◽  
Homozygous Mutant ◽  
Early Mouse ◽  
Mesoderm Patterning ◽  
Anterior Posterior ◽  
Anterior Visceral Endoderm

Recent embryological and genetic experiments have suggested that the anterior visceral endoderm and the anterior primitive streak of the early mouse gastrula function as head- and trunk-organising centers, respectively. Here, we report that HNF3beta and Lim1 are coexpressed in both organising centers suggesting synergistic roles of these genes in regulating organiser functions and hence axis development in the mouse embryo. To investigate this possibility, we generated compound HNF3beta and Lim1 mutant embryos. An enlarged primitive streak and a lack of axis formation were observed in HNF3beta (−)(/)(−);Lim1(−)(/)(−), but not in single homozygous mutant embryos. Chimera experiments indicate that the primary defect in these double homozygous mutants is due to loss of activity of HNF3beta and Lim1 in the visceral endoderm. Altogether, these data provide evidence that these genes function synergistically to regulate organiser activity of the anterior visceral endoderm. Moreover, HNF3beta (−)(/)(−);Lim1(−)(/)(−) mutant embryos also exhibit defects in mesoderm patterning that are likely due to lack of specification of anterior primitive streak cells.

Head induction in the chick by primitive endoderm of mammalian, but not avian origin

Development ◽  
1999 ◽  
Vol 126 (4) ◽  
pp. 815-825 ◽  
Author(s):  
H. Knoetgen ◽  
C. Viebahn ◽  
M. Kessel
Keyword(s):  
Lower Layer ◽  
Homeobox Gene ◽  
Primitive Streak ◽  
Neural Plate ◽  
Visceral Endoderm ◽  
Avian Origin ◽  
Bmp Antagonist ◽  
Rabbit Embryos ◽  
Inductive Potential ◽  
Anterior Visceral Endoderm

Different types of endoderm, including primitive, definitive and mesendoderm, play a role in the induction and patterning of the vertebrate head. We have studied the formation of the anterior neural plate in chick embryos using the homeobox gene GANF as a marker. GANF is first expressed after mesendoderm ingression from Hensen's node. We found that, after transplantation, neither the avian hypoblast nor the anterior definitive endoderm is capable of GANF induction, whereas the mesendoderm (young head process, prechordal plate) exhibits a strong inductive potential. GANF induction cannot be separated from the formation of a proper neural plate, which requires an intact lower layer and the presence of the prechordal mesendoderm. It is inhibited by BMP4 and promoted by the presence of the BMP antagonist Noggin. In order to investigate the inductive potential of the mammalian visceral endoderm, we used rabbit embryos which, in contrast to mouse embryos, allow the morphological recognition of the prospective anterior pole in the living, pre-primitive-streak embryo. The anterior visceral endoderm from such rabbit embryos induced neuralization and independent, ectopic GANF expression domains in the area pellucida or the area opaca of chick hosts. Thus, the signals for head induction reside in the anterior visceral endoderm of mammals whereas, in birds and amphibia, they reside in the prechordal mesendoderm, indicating a heterochronic shift of the head inductive capacity during the evolution of mammalia.

Otx2 is required for visceral endoderm movement and for the restriction of posterior signals in the epiblast of the mouse embryo

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 753-765 ◽  
Author(s):  
A. Perea-Gomez ◽  
K.A. Lawson ◽  
M. Rhinn ◽  
L. Zakin ◽  
P. Brulet ◽  
...  
Keyword(s):  
Essential Role ◽  
Homeobox Gene ◽  
Primitive Streak ◽  
Lineage Tracing ◽  
Secreted Proteins ◽  
Visceral Endoderm ◽  
Cellular Mechanisms ◽  
Cell Fates ◽  
Marker Studies ◽  
Anterior Visceral Endoderm

Genetic and embryological experiments have demonstrated an essential role for the visceral endoderm in the formation of the forebrain; however, the precise molecular and cellular mechanisms of this requirement are poorly understood. We have performed lineage tracing in combination with molecular marker studies to follow morphogenetic movements and cell fates before and during gastrulation in embryos mutant for the homeobox gene Otx2. Our results show, first, that Otx2 is not required for proliferation of the visceral endoderm, but is essential for anteriorly directed morphogenetic movement. Second, molecules that are normally expressed in the anterior visceral endoderm, such as Lefty1 and Mdkk1, are not expressed in Otx2 mutants. These secreted proteins have been reported to antagonise, respectively, the activities of Nodal and Wnt signals, which have a role in regulating primitive streak formation. The visceral endoderm defects of the Otx2 mutants are associated with abnormal expression of primitive streak markers in the epiblast, suggesting that anterior epiblast cells acquire primitive streak characteristics. Taken together, our data support a model whereby Otx2 functions in the anterior visceral endoderm to influence the ability of the adjacent epiblast cells to differentiate into anterior neurectoderm, indirectly, by preventing them from coming under the influence of posterior signals that regulate primitive streak formation.

Anterior patterning by synergistic activity of the early gastrula organizer and the anterior germ layer tissues of the mouse embryo

Development ◽  
1999 ◽  
Vol 126 (22) ◽  
pp. 5171-5179 ◽  
Author(s):  
P.P. Tam ◽  
K.A. Steiner
Keyword(s):  
Primitive Streak ◽  
Germ Layer ◽  
Synergistic Activity ◽  
Visceral Endoderm ◽  
Neural Genes ◽  
Anterior Patterning ◽  
Host Embryo ◽  
Early Gastrula ◽  
Host Tissues ◽  
Anterior Visceral Endoderm

Fragments of the germ layer tissues isolated from the early-primitive-streak (early-streak) stage mouse embryos were tested for axis induction activity by transplantation to late-gastrula (late-streak to early-bud) stage host embryos. The posterior epiblast fragment that contains the early gastrula organizer was able to recruit the host tissues to form an ectopic axis. However, the most anterior neural gene that was expressed in the ectopic axis was Krox20 that marks parts of the hindbrain, but markers of the mid- and forebrain (Otx2 and En1) were not expressed. Anterior visceral endoderm or the anterior epiblast alone did not induce any ectopic neural tissue. However, when these two anterior germ layer tissues were transplanted together, they can induce the formation of ectopic host-derived neural tissues but these tissues rarely expressed anterior neural genes and did not show any organization of an ectopic axis. Therefore, although the anterior endoderm and epiblast together may display some inductive activity, they do not act like a classical organizer. Induction of the anterior neural genes in the ectopic axis was achieved only when a combination of the posterior epiblast fragment, anterior visceral endoderm and the anterior epiblast was transplanted to the host embryo. The formation of anterior neural structures therefore requires the synergistic interaction of the early gastrula organizer and anterior germ layer tissues.

scholarly journals Climate Mobility and Development Cooperation

2021 ◽  
Author(s):  
Robert Stojanov ◽  
Sarah Rosengaertner ◽  
Alex de Sherbinin ◽  
Raphael Nawrotzki
Keyword(s):  
Climate Adaptation ◽  
Human Mobility ◽  
Climate Impacts ◽  
Development Cooperation ◽  
Climate Variability And Change ◽  
Policy Frameworks ◽  
And Migration ◽  
And Function ◽  
Role And Function

AbstractDevelopment cooperation actors have been addressing climate change as a cross-cutting issue and investing in climate adaptation projects since the early 2000s. More recently, as concern has risen about the potential impacts of climate variability and change on human mobility, development cooperation actors have begun to design projects that intentionally address the drivers of migration, including climate impacts on livelihoods. However, to date, we know little about the development cooperation’s role and function in responding to climate related mobility and migration. As such, the main aim of this paper is to outline the policy frameworks and approaches shaping development cooperation actors’ engagement and to identify areas for further exploration and investment. First, we frame the concept of climate mobility and migration and discuss some applicable policy frameworks that govern the issue from various perspectives; secondly, we review the toolbox of approaches that development cooperation actors bring to climate mobility; and third, we discuss the implications of the current Covid-19 pandemic and identify avenues for the way forward. We conclude that ensuring safe and orderly mobility and the decent reception and long-term inclusion of migrants and displaced persons under conditions of more severe climate hazards, and in the context of rising nationalism and xenophobia, poses significant challenges. Integrated approaches across multiple policy sectors and levels of governance are needed. In addition to resources, development cooperation actors can bring data to help empower the most affected communities and regions and leverage their convening power to foster more coordinated approaches within and across countries.

scholarly journals EMT Participates in the Regulation of Exosomes Secretion and Function in Esophageal Cancer Cells

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Chuangui Chen ◽  
Zhao Ma ◽  
Hongjing Jiang
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Promoting Effect ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
And Function ◽  
Esophageal Cancer Cells

Epithelial-mesenchymal transition (EMT) is a key step in tumor invasion and distant metastasis. Abundant evidence has documented that exosomes can mediate EMT of tumor cells and endow them with the ability of invasion and migration. However, there are few studies focusing on whether EMT can reverse the secretion of exosomes. In this study, 2 esophageal cancer cells (FLO-1 and SK-GT-4) were selected to compare the migration ability and EMT activation, and to further analyze the secretion ability of exosomes of the 2 cell lines. According to the results, inhibited activation of EMT in FLO-1 cells with relatively high migration ability could effectively reduce the secretion of exosomes. Besides, in SK-GT-4 cells, EMT activation induced by TGF-β could promote the secretion of exosomes. FLO-1 cell derived exosomes exhibited a paracrine effect of promoting the migration of SK-GT-4 cells, and the use of EMT inhibitors could weaken this ability. Furthermore, inhibition of EMT could change the relative content of some miRNAs in exosomes, with a particularly significant downregulation in the expression of miR-196-5p, miR-21-5p and miR-194-5p. Significantly, artificial transfection of the 3 miRNAs into exosomes by electroporation resulted in the recovery of migration-promoting effect of exosomes. Subsequent experiments further revealed that the effect of EMT on these miRNAs could be explained by the intracellular transcription level or the specific sorting mechanism of exosomes. To sum up, our study undoubtedly reveals that EMT has a regulatory effect on exosomes in the quantity and contents in esophageal cancer cells. Significantly, findings in our study provide experimental evidence for the interaction of EMT with the secretion and sorting pathway of exosomes, and also give a new direction for the further study of tumor metastasis.

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