Streak Formation Research Articles

Effect of Testosterone on Inflammatory Markers in the Development of Early Atherogenesis in the Testicular-Feminized Mouse Model

Background. Low levels of serum testosterone in men are associated with cardiovascular disease. Clinical studies show that testosterone replacement therapy (TRT) can improve symptoms of cardiovascular disease and reduce the inflammatory burden evident in atherosclerosis. Aim. We used an in vivo animal model to determine whether testosterone influences mediators of vascular inflammation as part of its beneficial effects on atherogenesis. Methods. Testicular-feminized (Tfm) mice, which express low endogenous testosterone and a non-functional androgen receptor (AR), were used to assess the effect of androgen status on atheroma formation, serum lipids, and inflammatory mediators. Tfm mice were fed a high-cholesterol diet, received saline or physiological (TRT), and were compared to saline-treated XY littermates. Results. A total of 28 weeks of high-cholesterol diet caused fatty streak formation in the aortic root of XY littermates and Tfm mice, an effect significantly amplified in Tfm mice. Tfm mice on normal diet showed elevated serum tumor necrosis factor-α (TFN-α) and interleukin-6 compared to XY littermates. High-cholesterol diet induced increased monocyte chemoattractant protein-1 (MCP-1) in Tfm mice, and TFN-α and MCP-1 in XY littermates. TRT reduced fatty streak formation and serum interleukin-6 in Tfm mice but had no significant effects on lipid profiles. Monocyte/macrophage staining indicated local inflammation in aortic root fatty streak areas of all mice, with TRT reducing local inflammation through plaque reduction in Tfm mice. Fractalkine (CX3CL1) and its receptor (CX3CR1) were present in fatty streaks of all mice fed a high-cholesterol diet, independent of androgen status. Conclusion. These results are consistent with AR-dependent and AR-independent anti-inflammatory actions of testosterone in atheroprotection, although the local anti-inflammatory mechanisms via which testosterone acts remain unknown.

Experimentally-Induced Metabolic Acidosis Does not Alter Aortic Fatty Streak Formation in High-Cholesterol Fed Rabbits.

Cardiovascular disease causes a major clinical problem in patients with end stage renal disease. Since metabolic acidosis is very common in patients with end stage renal disease, we aimed to investigate the effect of experimentally-induced metabolic acidosis on serum lipid profile and aortic fatty streak (FS) formation in normal and high-cholesterol fed rabbits. Twenty-four male rabbits were divided into four groups (n=6 each): (1) normal diet (ND): (2) hypercholesterolemic diet (HCD) (1%): (3) ND plus acidemic diet: (4) HCD plus acidemic diet. Metabolic acidosis was induced by adding 0.75% NH4Cl in drinking water. After 4 weeks, blood samples were taken and thoracic aortae were dissected for histological examinations. Results showed that in the animals who received NH4Cl, metabolic acidosis was successfully induced. Serum total cholesterol and low density lipoprotein (LDL) concentrations in HCD groups were significantly higher than ND groups (P<0.05) and acidosis did not significantly change serum lipid levels neither in ND nor in HCD animals (P>0.05). Histological examination of aortae showed higher mean average grades of pathological evaluation in HCD than ND groups (2.1±0.16 vs. 0±0; P<0.05). Acidosis did not further increase FS formation in HCD groups (P >0.05). In this model of experimentally-induced metabolic acidosis, acidosis could not increase FS formation in HCD animals and it seems that it does not interfere in progression of atherosclerosis process.

Gata2 provides an early anterior bias and uncovers a global positioning system for polarity in the amniote embryo

The first axis to be specified during vertebrate development is that between the site where gastrulation will begin and the opposite pole of the embryo (dorsoventral axis in amphibians and fish, anteroposterior in amniotes). This relies on Nodal activity, but different vertebrates differ in how this activity is positioned. In chick, the earliest known asymmetry is posterior expression of the TGFβ-related factor Vg1, close to the future Nodal expression domain. Here we show that the transcription factor Gata2 is expressed anteriorly before this stage. Gata2 influences the site of primitive streak formation and its role is independent from, and upstream of, Vg1 and Wnt. However, although Vg1 is required for streak formation, Gata2 does not act as an absolute anterior specifier, but provides an anterior bias. These findings point to previously unsuspected global determinants of polarity of the early amniote embryo.

High-sensitivity C-reactive protein as a biomarker of risk in coronary artery disease

Vascular inflammation plays a crucial role in the pathogenesis of atherosclerosis and mediates various stages of atherosclerotic plaque development, from lipid streak formation to the plaque rupture and destabilization that precedes the clinical syndromes of cardiovascular disease. Inflammatory biomarkers constitute valuable tools to study this process, enabling the effects of different therapeutic interventions to be assessed. Currently, C-reactive protein (CRP) determined by high-sensitivity methods (hs-CRP) is the most extensively studied biomarker. Data regarding hs-CRP and cardiovascular risk, though largely consistent, are of unclear clinical relevance. This article provides a comprehensive review of current knowledge concerning cardiovascular risk and hs-CRP, and concludes with an evidence-based analysis of the current role of hs-CRP in cardiovascular risk assessment.

Proteína C reativa de alta sensibilidade como biomarcador de risco na doença coronária

Vascular inflammation plays a crucial role in the pathogenesis of atherosclerosis and mediates various stages of atherosclerotic plaque development, from lipid streak formation to the plaque rupture and destabilization that precedes the clinical syndromes of cardiovascular disease. Inflammatory biomarkers constitute valuable tools to study this process, enabling the effects of different therapeutic interventions to be assessed. Currently, C-reactive protein (CRP) determined by high-sensitivity methods (hs-CRP) is the most extensively studied biomarker. Data regarding hs-CRP and cardiovascular risk, though largely consistent, are of unclear clinical relevance. This article provides a comprehensive review of current knowledge concerning cardiovascular risk and hs-CRP, and concludes with an evidence-based analysis of the current role of hs-CRP in cardiovascular risk assessment.

Spatiotemporal Mechanical Variation Reveals Critical Role for Rho Kinase During Primitive Streak Morphogenesis

Large-scale morphogenetic movements during early embryo development are driven by complex changes in biochemical and biophysical factors. Current models for amniote primitive streak morphogenesis and gastrulation take into account numerous genetic pathways but largely ignore the role of mechanical forces. Here, we used atomic force microscopy (AFM) to obtain for the first time precise biomechanical properties of the early avian embryo. Our data reveal that the primitive streak is significantly stiffer than neighboring regions of the epiblast, and that it is stiffer than the pre-primitive streak epiblast. To test our hypothesis that these changes in mechanical properties are due to a localized increase of actomyosin contractility, we inhibited actomyosin contractility via the Rho kinase (ROCK) pathway using the small-molecule inhibitor Y-27632. Our results using several different assays show the following: (1) primitive streak formation was blocked; (2) the time-dependent increase in primitive streak stiffness was abolished; and (3) convergence of epiblast cells to the midline was inhibited. Taken together, our data suggest that actomyosin contractility is necessary for primitive streak morphogenesis, and specifically, ROCK plays a critical role. To better understand the underlying mechanisms of this fundamental process, future models should account for the findings presented in this study.

Antagonism of Nodal signaling by BMP/Smad5 prevents ectopic primitive streak formation in the mouse amnion

The strength and spatiotemporal activity of Nodal signaling is tightly controlled in early implantation mouse embryos, including by autoregulation and feedback loops, and involves secreted and intracellular antagonists. These control mechanisms, which are established at the extra-embryonic/embryonic interfaces, are essential for anterior-posterior patterning of the epiblast and correct positioning of the primitive streak. Formation of an ectopic primitive streak, or streak expansion, has previously been reported in mutants lacking antagonists that target Nodal signaling. Here, we demonstrate that loss-of-function of a major bone morphogenetic protein (BMP) effector, Smad5, results in formation of an ectopic primitive streak-like structure in mutant amnion accompanied by ectopic Nodal expression. This suggests that BMP/Smad5 signaling contributes to negative regulation of Nodal. In cultured cells, we find that BMP-activated Smad5 antagonizes Nodal signaling by interfering with the Nodal-Smad2/4-Foxh1 autoregulatory pathway through the formation of an unusual BMP4-induced Smad complex containing Smad2 and Smad5. Quantitative expression analysis supports that ectopic Nodal expression in the Smad5 mutant amnion is induced by the Nodal autoregulatory loop and a slow positive-feedback loop. The latter involves BMP4 signaling and also induction of ectopic Wnt3. Ectopic activation of these Nodal feedback loops in the Smad5 mutant amnion results in the eventual formation of an ectopic primitive streak-like structure. We conclude that antagonism of Nodal signaling by BMP/Smad5 signaling prevents primitive streak formation in the amnion of normal mouse embryos.

Proatherogenic Macrophage Activities Are Targeted by the Flavonoid Quercetin

Many studies have demonstrated that the flavonoid quercetin protects against cardiovascular disease (CVD) and related risk factors. Atherosclerosis, the underlying cause of CVD, is also attenuated by oral quercetin administration in animal models. Although macrophages are key players during fatty streak formation and plaque progression and aggravation, little is known about the effects of quercetin on atherogenic macrophages. Here, we report that primary bone marrow-derived macrophages internalized less oxidized low-density lipoprotein (oxLDL) and accumulated less intracellular cholesterol in the presence of quercetin. This reduction of foam cell formation correlated with reduced surface expression of the oxLDL receptor CD36. Quercetin also targeted the lipopolysaccharide-dependent, oxLDL-independent pathway of lipid droplet formation in macrophages. In oxLDL-stimulated macrophages, quercetin inhibited reactive oxygen species production and interleukin (IL)-6 secretion. In a system that evaluated cholesterol crystal-induced IL-1β secretion via nucleotide-binding domain and leucine-rich repeat containing protein 3 inflammasome activation, quercetin also exhibited an inhibitory effect. Dyslipidemic apolipoprotein E-deficient mice chronically treated with intraperitoneal quercetin injections had smaller atheromatous lesions, reduced lipid deposition, and less macrophage and T cell inflammatory infiltrate in the aortic roots than vehicle-treated animals. Serum levels of total cholesterol and the lipid peroxidation product malondialdehyde were also reduced in these mice. Our results demonstrate that quercetin interferes with both key proatherogenic activities of macrophages, namely foam cell formation and pro-oxidant/proinflammatory responses, and these effects may explain the atheroprotective properties of this common flavonoid.

Hyperinsulinemia may have a protective role in the early stages of atherosclerosis in rabbit model of hypercholesterolemia

BackgroundHypercholesterolemia causes inflammation and insulin resistance in the vasculature. Previous data suggest that vascular endothelium is a physiological target of insulin. Dyslipidemia and atherosclerosis are disorders with endothelial dysfunction that are associated with an increased production of superoxide anion, and early deficit of nitric oxide (NO) production. We examined alteration of plasma levels of insulin, C-reactive protein (CRP) and total NO metabolites (NOx), as well as fatty streak formation in the rabbit model of hypercholesterolemia.MethodsWhite male rabbits were fed either a high-cholesterol diet (HC; 1% cholesterol, n = 6) or control diet (c, n = 6) for one month. The serum levels of Cholesterol, LDL, HDL, NOx, insulin and CRP were measured before and after study. By the end of study, rabbits' aorta was explored for fatty streak formation.ResultsThe cholesterol-rich diet induced a significant increase in total cholesterol, LDL, and HDL as well as fatty streak lesions in HC group while there were no significant changes of these parameters in control group (p <0.05). There was significant difference in plasma levels of CRP, insulin and total NO metabolite between two groups of experiment. Negative significant correlation of CRP and insulin also was observed in HC rabbits (r = −0.99, p <0.05).ConclusionParallel NOx and insulin increment and negative correlation of CRP and insulin in HC rabbits may be suggestive a protective role of hyperinsulinemia in early atherosclerosis.

‘Melt welt’ mechanism of extreme weakening of gabbro at seismic slip rates

Laboratory studies of frictional properties of rocks at slip velocities approaching the seismic range (∼0.1-1 m s(-1)), and at moderate normal stresses (1-10 MPa), have revealed a complex evolution of the dynamic shear strength, with at least two phases of weakening separated by strengthening at the onset of wholesale melting. The second post-melting weakening phase is governed by viscous properties of the melt layer and is reasonably well understood. The initial phase of extreme weakening, however, remains a subject of much debate. Here we show that the initial weakening of gabbro is associated with the formation of hotspots and macroscopic streaks of melt ('melt welts'), which partially unload the rest of the slip interface. Melt welts begin to form when the average rate of frictional heating exceeds 0.1-0.4 MW m(-2), while the average temperature of the shear zone is well below the solidus (250-450 °C). Similar heterogeneities in stress and temperature are likely to occur on natural fault surfaces during rapid slip, and to be important for earthquake rupture dynamics.

Control of growth and inflammatory response of macrophages and foam cells with nanotopography

Macrophages play an important role in modulating the immune function of the human body, while foam cells differentiated from macrophages with subsequent fatty streak formation play a key role in atherosclerosis. We hypothesized that nanotopography modulates the behavior and function of macrophages and foam cells without bioactive agent. In the present study, nanodot arrays ranging from 10‐ to 200‐nm were used to evaluate the growth and function of macrophages and foam cells. In the quantitative analysis, the cell adhesion area in macrophages increased with 10- to 50-nm nanodot arrays compared to the flat surface, while it decreased with 100- and 200-nm nanodot arrays. A similar trend of adhesion was observed in foam cells. Immunostaining, specific to vinculin and actin filaments, indicated that a 50-nm surface promoted cell adhesion and cytoskeleton organization. On the contrary, 200-nm surfaces hindered cell adhesion and cytoskeleton organization. Further, based on quantitative real-time polymerase chain reaction data, expression of inflammatory genes was upregulated for the 100- and 200-nm surfaces in macrophages and foam cells. This suggests that nanodots of 100‐ and 200‐nm triggered immune inflammatory stress response. In summary, nanotopography controls cell morphology, adhesions, and proliferation. By adjusting the nanodot diameter, we could modulate the growth and expression of function-related genes in the macrophages and foam cell system. The nanotopography-mediated control of cell growth and morphology provides potential insight for designing cardiovascular implants.

파형벽면이 있는 채널 유동의 응집 구조 연구

The present study focuses on the case of developing flow with in a channel containing a long array of sinusoidal waves (2a/<TEX>${\lambda}$</TEX>=0.1, <TEX>${\lambda}$</TEX>=h, <TEX>${\lambda}$</TEX> is the wavelength, 2a is the wave height, h is the mean channel depth) at the bottom wall. The Reynolds number defined with channel height, h and the mean velocity, U, is Re=6,700. The channel is sufficiently long such that transition is completed and the flow is fully developed over the downstream half of the channel. For the case of an incoming steady flow with no resolved turbulence, the instantaneous flow fields in the transition region are characterized by the formation of arrays of highly-organized large-scale hairpin vortices whose dimensions scale with that of the roughness elements. The paper explains the mechanism for the formation of these arrays of hairpin vortices and shows these eddies play the primary role in the formation of the large-scale streaks of high and low velocity over the wavy wall region. The presence of resolved turbulence in the incoming flow, reduces the streamwise distance needed for the streaks to develop over the wavy region, but does not affect qualitatively the transition process. In the fully-developed region, isolated and trains of large-scale hairpins play an important role in the dynamics of the streaks over the wavy wall.

Primitive Erythropoiesis Is Regulated by miR-126 via Nonhematopoietic Vcam-1+ Cells

Primitive erythropoiesis defines the onset of hematopoiesis in the yolk sac of the early embryo and is initiated by the emergence of progenitors assayed as colony-forming cells (EryP-CFCs). EryP-CFCs are detected for only a narrow window during embryonic development, suggesting that both their initiation and termination are tightly controlled. Using the embryonic stem differentiation system to model primitive erythropoiesis, we found that miR-126 regulates the termination of EryP-CFC development. Analyses of miR-126 null embryos revealed that thismiR also regulates EryP-CFCs invivo. We identified vascular cell adhesion molecule-1 (Vcam-1) expressed by a mesenchymal cell population asa relevant target of miR-126. Interaction of EryP-CFCs with Vcam-1 accelerated their maturation to ßh1-globin(+) and Ter119(+) cells through a Src family kinase. These findings uncover a cell nonautonomous regulatory pathway for primitive erythropoiesis that may provide insight into the mechanism(s) controlling the developmental switch from primitive to definitive hematopoiesis.

Yin-Yang1 is required for epithelial-to-mesenchymal transition and regulation of Nodal signaling during mammalian gastrulation

The ubiquitously expressed Polycomb Group protein Yin-Yang1 (YY1) is believed to regulate gene expression through direct binding to DNA elements found in promoters or enhancers of target loci. Additionally, YY1 contains diverse domains that enable a plethora of protein–protein interactions, including association with the Oct4/Sox2 pluripotency complex and Polycomb Group silencing complexes. To elucidate the in vivo role of YY1 during gastrulation, we generated embryos with an epiblast specific deletion of Yy1. Yy1 conditional knockout (cKO) embryos initiate gastrulation, but both primitive streak formation and ingression through the streak is severely impaired. These streak descendants fail to repress E-Cadherin and are unable to undergo an appropriate epithelial to mesenchymal transition (EMT). Intriguingly, overexpression of Nodal and concomitant reduction of Lefty2 are observed in Yy1 cKO embryos, suggesting that YY1 is normally required for proper Nodal regulation during gastrulation. Furthermore, definitive endoderm is specified but fails to properly integrate into the outer layer. Although anterior neuroectoderm is specified, mesoderm production is severely restricted. We show that YY1 directly binds to the Lefty2 locus in E7.5 embryos and that pharmacological inhibition of Nodal signaling partially restores mesoderm production in Yy1 cKO mutant embryos. Our results reveal critical requirements for YY1 during several important developmental processes, including EMT and regulation of Nodal signaling. These results are the first to elucidate the diverse role of YY1 during gastrulation in vivo.

Radar observations of individual rain drops in the free atmosphere

Atmospheric remote sensing has played a pivotal role in the increasingly sophisticated representation of clouds in the numerical models used to assess global and regional climate change. This has been accomplished because the underlying bulk cloud properties can be derived from a statistical analysis of the returned microwave signals scattered by a diverse ensemble comprised of numerous cloud hydrometeors. A new Doppler radar, previously used to track small debris particles shed from the NASA space shuttle during launch, is shown to also have the capacity to detect individual cloud hydrometeors in the free atmosphere. Similar to the traces left behind on film by subatomic particles, larger cloud particles were observed to leave a well-defined radar signature (or streak), which could be analyzed to infer the underlying particle properties. We examine the unique radar and environmental conditions leading to the formation of the radar streaks and develop a theoretical framework which reveals the regulating role of the background radar reflectivity on their observed characteristics. This main expectation from theory is examined through an analysis of the drop properties inferred from radar and in situ aircraft measurements obtained in two contrasting regions of an observed multicellular storm system. The observations are placed in context of the parent storm circulation through the use of the radar's unique high-resolution waveforms, which allow the bulk and individual hydrometeor properties to be inferred at the same time.

Distinct gene expression signatures in human embryonic stem cells differentiated towards definitive endoderm at single-cell level

Characterization of directed differentiation of pluripotent stem cells towards therapeutically relevant cell types, including pancreatic beta-cells and hepatocytes, depends on molecular markers and assays that resolve the signature of individual cells. Pancreas and liver both have a common origin of anterior definitive endoderm (DE). Here, we differentiated human embryonic stem cells towards DE using three different activin A based treatments. Differentiation efficiencies were evaluated by gene expression profiling over time at cell population level. A panel of key markers was used to study DE formation. Final DE differentiation was also analyzed with immunocytochemistry and single-cell gene expression profiling. We found that cells treated with activin A in combination with sodium butyrate and B27 serum-free supplement medium generated the most mature DE cells. Cell population studies were useful to monitor the temporal expression of genes involved in primitive streak formation and endoderm formation, while single-cell analysis allowed us to study cell culture heterogeneity and fingerprint individual cells. In addition, single-cell analysis revealed distinct gene expression patterns for the three activin A based protocols applied. Our data provide novel insights in DE gene expression at the cellular level of in vitro differentiated human embryonic stem cells, and illustrate the power of using single-cell gene expression profiling to study differentiation heterogeneity and to characterize cell types and subpopulations.

A long-lived band of plasma density enhancement at mid-latitudes during the 2003 Halloween magnetic storm

During the magnetic storm recovery phase between 08 and 13 UT on 30th October 2003 (so-called Halloween Storm), CHAMP, GRACE and TIMED satellites encountered an unusual post-midnight streak of high plasma density. The streak was latitudinally narrow (∼0.5° GLAT), zonally elongated (>10° GLON), and vertically extended for several hundred kilometers. Inside the streak, as observed by CHAMP, the deviation of the magnetic field from the background is greater in the zonal component than in the meridional component. This observation is consistent with the zonally extended nature of the streak, as confirmed by TIMED/GUVI optical observations. The field-aligned current (FAC) direction is generally upward (downward) at the equatorward (poleward) edge of the streak. We discuss the time history of observed features. We suggest the following scenario of the streak formation. A storm-enhanced density (SED) was generated before 19 h local time by a sub-auroral polarization stream (SAPS). The SED gradually separated from the poleward-retreating region of strong westward plasma drift and turned into an electron density enhancement fossil (EDEF). This EDEF at mid-latitude (about 40°S MLAT) practically co-rotated with the Earth for more than 10 h through the night till dawn. We suggest that the enhanced plasma pressure was counter-balanced by magnetic pressure gradient and kept stable over many hours.

Effect of chronic L-Arginine supplementation on aortic fatty streak formation and serum nitric oxide concentration in normal and high-cholesterol fed rabbits

Several reports indicated the beneficial effects of short-term L-Arginine (L-Arg) administration on atherosclerosis processes. The aim of this study was to evaluate the effect of chronic L-Arg supplementation on serum lipid profile, aortic Fatty Streak (FS) formation, and serum Nitric oxide (NO) concentration in Normal Diet (ND) and High-Cholesterol Diet (HCD) fed rabbits. 24 male rabbits were randomly divided into four groups (n=6 in each group) (i): ND for seven months; (ii): ND for 1 month plus ND + L-Arg for six months; (iii): HCD (1%) for 1 month plus HCD (0.5%) for six months; (iv): HCD (1%) for 1 month plus HCD (0.5%) + L-Arg for six months. At the end of the study, histological evaluation of aortic FS formation was performed. Blood samples were taken for serum lipid profile and NO concentrations. L-Arg did not change serum total cholesterol, triglyceride, LDL and LDL/HDL ratio in normal and hypercholesterolemic rabbits (p>0.05). Histological examination of thoracic aortae revealed that the HCD group had higher FS formation compared to the ND group (2.1 ± 0.16 vs. 0 ± 0; respectively; p<0.05) and L-Arg supplementation did not attenuate FS formation in the HCD group (1.93 ± 0.17 compare to 2.1 ± 0.16; p>0.05). Serum NO level in the HCD group was higher than ND groups (p<0.05). Chronic L-Arg supplementation did not alter serum NO concentration either in the hypercholesterolemic or in the ND group (p>0.05). It seems that chronic L-Arg supplementation does not have beneficial effects on aortic fatty streak formation, serum lipids and NO concentrations in this model of experimental hypercholesterolemia.

Ice Adhesion Tests on Pliable Polymer Sheets for Protection Against Sea-Water Spray Icing

Heavy sea-water spray icing is a major problem in the maintenance of lighthouses situated in northern harbors facing the Sea of Japan. Moreover, low ice adhesion materials or anti-icing coatings are ineffective over long periods. In this study, we have investigated the characteristics of saline ice adhesion on hydrophilic and hydrophobic pliable polymer sheets that can be used to envelop and thereby protect small lighthouses. We conducted experiments in cold room laboratories, and further, we verified the deicing conditions. Ice adhesion strength tests using fresh water indicated that a highly hydrophobic surface exhibited lower adhesion strength than other test materials. The results of saline ice adhesion tests at −20°C indicated that the adhesion strength decreases very rapidly as the salinity increases for all materials; this trend was particularly remarkable in case of superhydrophilic materials. The water spray icing tests were verified by experiments conducted using an ice model basin. Wet growth of ice occurred on all test specimens including the highly hydrophobic sheets. Furthermore, the initial icing depended significantly on the hydrophobic or hydrophilic surface properties. The icing on the hydrophobic surface was characterized by the formation of vertical streaks of ice; irregular projections could be observed on the ice surface. On the other hand, a thin fluid flow was formed on superhydrophilic surfaces. Exfoliation of pieces of the sheet ice was often observed during the initial growth. Deicing could be easily performed for both pliable polymer sheets. A combination of low ice adhesion property and rapid distortion was effective for the deicing of sea-water spray icing.

The hypoblast (visceral endoderm): an evo-devo perspective.

When amniotes appeared during evolution, embryos freed themselves from intracellular nutrition; development slowed, the mid-blastula transition was lost and maternal components became less important for polarity. Extra-embryonic tissues emerged to provide nutrition and other innovations. One such tissue, the hypoblast (visceral endoderm in mouse), acquired a role in fixing the body plan: it controls epiblast cell movements leading to primitive streak formation, generating bilateral symmetry. It also transiently induces expression of pre-neural markers in the epiblast, which also contributes to delay streak formation. After gastrulation, the hypoblast might protect prospective forebrain cells from caudalizing signals. These functions separate mesendodermal and neuroectodermal domains by protecting cells against being caught up in the movements of gastrulation.