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Journal ArticleDOI

Integrin β1 coordinates survival and morphogenesis of the embryonic lineage upon implantation and pluripotency transition.

TL;DR: In this article, the authors studied integrin β1 signaling, as embryos deficient for this receptor degenerate at implantation and demonstrated that the coordinated action of pro-survival signals and localized actomyosin suppression via integrinβ1 permits the development of the embryo beyond implantation.
About: This article is published in Cell Reports.The article was published on 2021-03-09 and is currently open access. It has received 21 citations till now. The article focuses on the topics: Epiblast & Fibroblast growth factor.
Citations
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Journal ArticleDOI
TL;DR: The role of apical-basal polarity in epithelial cell formation and function has been investigated in this article , where the authors reveal the dynamic interactions between polarity factors and how they contribute to polarity establishment and maintenance.
Abstract: Epithelial cells are the most common cell type in all animals, forming the sheets and tubes that compose most organs and tissues. Apical–basal polarity is essential for epithelial cell form and function, as it determines the localization of the adhesion molecules that hold the cells together laterally and the occluding junctions that act as barriers to paracellular diffusion. Polarity must also target the secretion of specific cargoes to the apical, lateral or basal membranes and organize the cytoskeleton and internal architecture of the cell. Apical–basal polarity in many cells is established by conserved polarity factors that define the apical (Crumbs, Stardust/PALS1, aPKC, PAR-6 and CDC42), junctional (PAR-3) and lateral (Scribble, DLG, LGL, Yurt and RhoGAP19D) domains, although recent evidence indicates that not all epithelia polarize by the same mechanism. Research has begun to reveal the dynamic interactions between polarity factors and how they contribute to polarity establishment and maintenance. Elucidating these mechanisms is essential to better understand the roles of apical–basal polarity in morphogenesis and how defects in polarity contribute to diseases such as cancer. Apical–basal polarity is essential for epithelial cell form and function. Elucidating how distinct apical and basolateral compartments are established and maintained is essential to better understand the roles of apical–basal cell polarization in morphogenesis and how defects in polarity contribute to diseases such as cancer.

52 citations

Journal ArticleDOI
TL;DR: In this article, the authors examined these recent findings in light of our knowledge of peri-implantation mouse and human development, and considered the implications of this work for deriving human embryo models from pluripotent cells.

26 citations

Journal ArticleDOI
30 Jul 2021
TL;DR: In this paper, a review of physical principles that play a role in the growth and coarsening of lumens is presented, focusing on the relevant force, time and length scales involved in these processes.
Abstract: Asbtract Lumen formation plays an essential role in the morphogenesis of tissues during development. Here we review the physical principles that play a role in the growth and coarsening of lumens. Solute pumping by the cell, hydraulic flows driven by differences of osmotic and hydrostatic pressures, balance of forces between extracellular fluids and cell-generated cytoskeletal forces, and electro-osmotic effects have been implicated in determining the dynamics and steady-state of lumens. We use the framework of linear irreversible thermodynamics to discuss the relevant force, time and length scales involved in these processes. We focus on order of magnitude estimates of physical parameters controlling lumen formation and coarsening.

16 citations

Journal ArticleDOI
TL;DR: In this paper , a stem cell-specific cadherin code was proposed to drive synthetic embryogenesis, which can self-assemble into synthetic embryos by exploiting lineage-specific stem cells from different stages of development.
Abstract: Abstract Mammalian embryos sequentially differentiate into trophectoderm and an inner cell mass, the latter of which differentiates into primitive endoderm and epiblast. Trophoblast stem (TS), extraembryonic endoderm (XEN) and embryonic stem (ES) cells derived from these three lineages can self-assemble into synthetic embryos, but the mechanisms remain unknown. Here, we show that a stem cell-specific cadherin code drives synthetic embryogenesis. The XEN cell cadherin code enables XEN cell sorting into a layer below ES cells, recapitulating the sorting of epiblast and primitive endoderm before implantation. The TS cell cadherin code enables TS cell sorting above ES cells, resembling extraembryonic ectoderm clustering above epiblast following implantation. Whereas differential cadherin expression drives initial cell sorting, cortical tension consolidates tissue organization. By optimizing cadherin code expression in different stem cell lines, we tripled the frequency of correctly formed synthetic embryos. Thus, by exploiting cadherin codes from different stages of development, lineage-specific stem cells bypass the preimplantation structure to directly assemble a postimplantation embryo.

9 citations

Journal ArticleDOI
TL;DR: In this article , the small GTPase Rap1 plays a critical role in reshaping the pluripotent lineage, which enables de novo epithelialization and formation of tricellular junctions in the epiblast.

7 citations

References
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Journal ArticleDOI
TL;DR: Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis that facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system.
Abstract: Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis. Fiji uses modern software engineering practices to combine powerful software libraries with a broad range of scripting languages to enable rapid prototyping of image-processing algorithms. Fiji facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system. We propose Fiji as a platform for productive collaboration between computer science and biology research communities.

43,540 citations

Journal ArticleDOI
TL;DR: A central question in cell biology is how membrane-spanning receptors transmit extracellular signals inside cells to modulate cell adhesion and motility.
Abstract: A central question in cell biology is how membrane-spanning receptors transmit extracellular signals inside cells to modulate cell adhesion and motility. Focal adhesion kinase (FAK) is a crucial signalling component that is activated by numerous stimuli and functions as a biosensor or integrator to control cell motility. Through multifaceted and diverse molecular connections, FAK can influence the cytoskeleton, structures of cell adhesion sites and membrane protrusions to regulate cell movement.

2,361 citations

Journal ArticleDOI
TL;DR: Application of a selective Rho-associated kinase (ROCK) inhibitor, Y-27632, to hES cells markedly diminishes dissociation-induced apoptosis, increases cloning efficiency and facilitates subcloning after gene transfer, and enables SFEB-cultured hES Cells to survive and differentiate into Bf1+ cortical and basal telencephalic progenitors.
Abstract: Poor survival of human embryonic stem (hES) cells after cell dissociation is an obstacle to research, hindering manipulations such as subcloning. Here we show that application of a selective Rho-associated kinase (ROCK) inhibitor1,2, Y-27632, to hES cells markedly diminishes dissociation-induced apoptosis, increases cloning efficiency (from ∼1% to ∼27%) and facilitates subcloning after gene transfer. Furthermore, dissociated hES cells treated with Y-27632 are protected from apoptosis even in serum-free suspension (SFEB) culture3 and form floating aggregates. We demonstrate that the protective ability of Y-27632 enables SFEB-cultured hES cells to survive and differentiate into Bf1+ cortical and basal telencephalic progenitors, as do SFEB-cultured mouse ES cells.

2,094 citations

Journal ArticleDOI
TL;DR: The total rate of pregnancy loss after implantation, including clinically recognized spontaneous abortions, was 31 percent and most of the 40 women with unrecognized early pregnancy losses had normal fertility, since 95 percent of them subsequently became clinically pregnant within two years.
Abstract: We studied the risk of early loss of pregnancy by collecting daily urine specimens from 221 healthy women who were attempting to conceive. Urinary concentrations of human chorionic gonadotropin (hCG) were measured for a total of 707 menstrual cycles with use of an immunoradiometric assay that is able to detect hCG levels as low as 0.01 ng per milliliter, with virtually 100 percent specificity for hCG in the presence of luteinizing hormone. Our criterion for early pregnancy--an hCG level above 0.025 ng per milliliter on three consecutive days--was determined after we compared the hCG levels in the study group with the levels in a comparable group of 28 women who had undergone sterilization by tubal ligation. We identified 198 pregnancies by an increase in the hCG level near the expected time of implantation. Of these, 22 percent ended before pregnancy was detected clinically. Most of these early pregnancy losses would not have been detectable by the less sensitive assays for hCG used in earlier studies. The total rate of pregnancy loss after implantation, including clinically recognized spontaneous abortions, was 31 percent. Most of the 40 women with unrecognized early pregnancy losses had normal fertility, since 95 percent of them subsequently became clinically pregnant within two years.

1,926 citations

Journal ArticleDOI
TL;DR: This review summarizes current information about these steps, including some of the molecular mechanisms that mediate them and how they may go awry, with consequent loss of the pregnancy.
Abstract: The implantation of fertilized ova and the formation of the placenta are crucial steps in reproduction. This review summarizes current information about these steps, including some of the molecular mechanisms that mediate them and how they may go awry, with consequent loss of the pregnancy.

1,086 citations

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