scholarly journals Mapping cell migrations and fates from a gastruloid model to the human primitive streak

2019 ◽  
Author(s):  
I. Martyn ◽  
E.D. Siggia ◽  
A.H. Brivanlou
Keyword(s):  
Mouse Embryo ◽  
Cell Tracking ◽  
Primitive Streak ◽  
Parallel Analysis ◽  
Self Organization ◽  
Model Organisms ◽  
Fate Map ◽  
Dependent Cell ◽  
Early Gastrula ◽  
Anterior Posterior

AbstractAlthough fate maps of early gastrula embryos exist for nearly all model organisms, a fate map of the gastrulating human embryo remains elusive. Here we use human gastruloids to piece together part of a rudimentary fate map of the human primitive streak (PS). This is possible because stimulation with differing levels of BMP, WNT, and NODAL leads to self-organization of gastruloids into large and homogenous different subpopulations of endoderm and mesoderm, and comparative parallel analysis of these gastruloids, together with the fate map of the mouse embryo, allows the organization of these subpopulations along an anterior-posterior axis. We also developed a novel cell tracking technique that allowed the detection of robust fate-dependent cell migrations in our gastruloids comparable to those found in the mouse embryo. Taken together, our gastruloid derived fate map and recording of cell migrations provides a first coarse view of the embryonic human PS.

scholarly journals Spatiotemporal sequence of mesoderm and endoderm lineage segregation during mouse gastrulation

2020 ◽  
Author(s):  
Simone Probst ◽  
Sagar ◽  
Jelena Tosic ◽  
Carsten Schwan ◽  
Dominic Grün ◽  
...  
Keyword(s):  
Mouse Embryo ◽  
Primitive Streak ◽  
Cell Types ◽  
Complete Separation ◽  
Embryonic Cell ◽  
Spatiotemporal Pattern ◽  
Cell Lineages ◽  
Dependent Cell ◽  
Summary Statement ◽  
Germ Layer Formation

AbstractAnterior mesoderm (AM) and definitive endoderm (DE) progenitors represent the earliest embryonic cell types that are specified during germ layer formation at the primitive streak (PS) of the mouse embryo. Genetic experiments indicate that both lineages segregate from Eomes expressing progenitors in response to different NODAL signaling levels. However, the precise spatiotemporal pattern of the emergence of these cell types and molecular details of lineage segregation remain unexplored. We combined genetic fate labeling and imaging approaches with scRNA-seq to follow the transcriptional identities and define lineage trajectories of Eomes dependent cell types. All cells moving through the PS during the first day of gastrulation express Eomes. AM and DE specification occurs before cells leave the PS from discrete progenitor populations that are generated in distinct spatiotemporal patterns. Importantly, we don’t find evidence for the existence of progenitors that co-express markers of both cell lineages suggesting an immediate and complete separation of AM and DE lineages.Summary statementCells lineages are specified in the mouse embryo already within the primitive streak where Mesp1+ mesoderm and Foxa2+ endoderm are generated in a spatial and temporal sequence from unbiased progenitors.

Embryonic axis orientation in the mouse and its correlation with blastocyst relationships to the uterus

Development ◽  
1985 ◽  
Vol 89 (1) ◽  
pp. 15-35
Author(s):  
L. J. Smith
Keyword(s):  
Mouse Embryo ◽  
Three Dimensional ◽  
Primitive Streak ◽  
Positional Information ◽  
Uterine Horn ◽  
The Other ◽  
Dimensional System ◽  
Fate Map ◽  
Axis Orientation ◽  
Three Dimensional System

Each of the three primary axes of the primitive streak (6¾ days p.c.) to C-shaped (9½ days) stage mouse embryo has a specific relationship to the uterine horn axes. By a retrograde analysis of younger sectioned embryos it has been possible to construct an axis fate map for the implanting 4¼-day blastocyst and to show how its implantation in one or the other of two specific orientations to the ends and walls of the horn leads to these embryo-horn relationships. The implanting blastocyst axis fate map can be related to an axis fate map of the attached blastocyst (Smith, 1980) since these too are in one or the other of two orientations to the ends and walls of the horn. It is suggested that the asymmetries of the attached and implanting blastocysts that allowed the distinctive attachment and implantation orientations to be recognized, are the initial expressions of a three-dimensional system of positional information that is present in the attached blastocyst.

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.

scholarly journals Control of early anterior-posterior patterning in the mouse embryo by TGF-β signalling

2003 ◽  
Vol 358 (1436) ◽  
pp. 1351-1358 ◽  
Author(s):  
Elizabeth J. Robertson ◽  
Dominic P. Norris ◽  
Jane Brennan ◽  
Elizabeth K. Bikoff
Keyword(s):  
Mouse Embryo ◽  
Transforming Growth Factor ◽  
Organizer Region ◽  
Primitive Streak ◽  
Transforming Growth Factor Β ◽  
Axis Formation ◽  
Posterior Side ◽  
Molecular Pattern ◽  
Discrete Population ◽  
Anterior Posterior

Prior to gastrulation the mouse embryo exists as a symmetrical cylinder consisting of three tissue layers. Positioning of the future anterior–posterior axis of the embryo occurs through coordinated cell movements that rotate a pre–existing proximal–distal (P–D) axis. Overt axis formation becomes evident when a discrete population of proximal epiblast cells become induced to form mesoderm, initiating primitive streak formation and marking the posterior side of the embryo. Over the next 12–24 h the primitive streak gradually elongates along the posterior side of the epiblast to reach the distal tip. The most anterior streak cells comprise the ‘organizer’ region and include the precursors of the so–called ‘axial mesendoderm’, namely the anterior definitive endoderm and prechordal plate mesoderm, as well as those cells that give rise to the morphologically patent node. Signalling pathways controlled by the transforming growth factor–β ligand nodal are involved in orchestrating the process of axis formation. Embryos lacking nodal activity arrest development before gastrulation, reflecting an essential role for nodal in establishing P–D polarity by generating and maintaining the molecular pattern within the epiblast, extraembryonic ectoderm and the visceral endoderm. Using a genetic strategy to manipulate temporal and spatial domains of nodal expression reveals that the nodal pathway is also instrumental in controlling both the morphogenetic movements required for orientation of the final axis and for specification of the axial mesendoderm progenitors.

Hematopoietic induction and respecification of A-P identity by visceral endoderm signaling in the mouse embryo

Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 5009-5018 ◽  
Author(s):  
M. Belaoussoff ◽  
S.M. Farrington ◽  
M.H. Baron
Keyword(s):  
Mouse Embryo ◽  
Decisive Role ◽  
Primitive Streak ◽  
Explant Culture ◽  
Cell Contact ◽  
Primitive Endoderm ◽  
Cell Fates ◽  
Posterior Aspect ◽  
Anterior Posterior

The anteroposterior axis of the developing embryo becomes morphologically apparent at the onset of gastrulation with the formation of the primitive streak. This structure, where the first mesodermal cells arise, marks the posterior aspect of the embryo. To examine the potential role of non-mesodermal signals in specifying posterior (hematopoietic and endothelial) cell fates in the mouse embryo, we have devised a transgenic explant culture system. We show that interactions between primitive endoderm and adjacent embryonic ectoderm or nascent mesoderm are required early in gastrulation for initiation of hematopoiesis and vasculogenesis. Surprisingly, primitive endoderm signals can respecify anterior (prospective neural) ectoderm to a posterior mesodermal fate, resulting in formation of blood and activation of endothelial markers. Reprogramming of anterior ectoderm does not require cell contact and is effected by stage-dependent, short-range, diffusible signal(s). Therefore, primitive endoderm signaling is a critical early determinant of hematopoietic and vascular development and plays a decisive role in anterior-posterior patterning during mouse embryogenesis.

scholarly journals Data-driven modeling reveals cell behaviors controlling self-organization during Myxococcus xanthus development

2017 ◽  
Vol 114 (23) ◽  
pp. E4592-E4601 ◽  
Author(s):  
Christopher R. Cotter ◽  
Heinz-Bernd Schüttler ◽  
Oleg A. Igoshin ◽  
Lawrence J. Shimkets
Keyword(s):  
Cell Tracking ◽  
Myxococcus Xanthus ◽  
Cell Movement ◽  
Modeling Method ◽  
Data Driven ◽  
Self Organization ◽  
Emergent Properties ◽  
Developmental Cycle ◽  
Fluorescent Cell ◽  
Cell Behaviors

Collective cell movement is critical to the emergent properties of many multicellular systems, including microbial self-organization in biofilms, embryogenesis, wound healing, and cancer metastasis. However, even the best-studied systems lack a complete picture of how diverse physical and chemical cues act upon individual cells to ensure coordinated multicellular behavior. Known for its social developmental cycle, the bacterium Myxococcus xanthus uses coordinated movement to generate three-dimensional aggregates called fruiting bodies. Despite extensive progress in identifying genes controlling fruiting body development, cell behaviors and cell–cell communication mechanisms that mediate aggregation are largely unknown. We developed an approach to examine emergent behaviors that couples fluorescent cell tracking with data-driven models. A unique feature of this approach is the ability to identify cell behaviors affecting the observed aggregation dynamics without full knowledge of the underlying biological mechanisms. The fluorescent cell tracking revealed large deviations in the behavior of individual cells. Our modeling method indicated that decreased cell motility inside the aggregates, a biased walk toward aggregate centroids, and alignment among neighboring cells in a radial direction to the nearest aggregate are behaviors that enhance aggregation dynamics. Our modeling method also revealed that aggregation is generally robust to perturbations in these behaviors and identified possible compensatory mechanisms. The resulting approach of directly combining behavior quantification with data-driven simulations can be applied to more complex systems of collective cell movement without prior knowledge of the cellular machinery and behavioral cues.

scholarly journals BMP4-induced symmetry breaking in a 3D model of the human epiblast

2019 ◽  
Author(s):  
Mijo Simunovic ◽  
Ali H. Brivanlou ◽  
Eric D. Siggia
Keyword(s):  
Live Cell Imaging ◽  
3D Model ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Imaging ◽  
Embryonic Stem ◽  
Primitive Streak ◽  
Mesenchymal Transition ◽  
Pluripotency Markers ◽  
Anterior Posterior

Abstract We describe the protocol of generating a 3D stem-cell-based model of the human pre-gastrulation epiblast by culturing human embryonic stem cells in a mix of hydrogel and Matrigel. Much like the epiblast of an in vitro attached day-10 human embryo, this model is an epithelial sphere with a cavity at its center, it is expressing key pluripotency markers, and it displays apico-basal polarity. The 3D colonies can further be differentiated with morphogens and in the case of intermediate concentrations of BMP4, they break the anterior-posterior symmetry characterized by an asymmetric expression of a primitive streak marker and showing signs of epithelial to mesenchymal transition. The protocol described here is suitable for immunofluorescence staining and for live-cell imaging.

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