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At least 19 recordsLinked to original sources
PubMed1978

[Comparative study of mouse teratoids developed from blastocysts and embryos at the three germ layer stage].

Germs of three stages: blasocyst, three layer germ cylinder, as well as head-fold and neural plate were implanted under the testicular capsule of mice, CBAXC57Bl line. Teratoids developed at the place of implantation are represented by the derivatives of all germ layers, as well as by some organic structures. The method for an experimental production of teratoids by means of transplantation of developing embryos is discussed as one of the methods for experimental histology. At the same time, possible tissue determination in embryos which do not undergo normal gastrulation is considered.

Animals↗
PubMed2025

Foxi2 and Sox3 are master regulators controlling ectoderm germ layer specification.

In vertebrates, germ layer specification represents a critical transition where pluripotent cells acquire lineage-specific identities. We identify the maternal transcription factors Foxi2 and Sox3 to be pivotal master regulators of ectodermal germ layer specification in Xenopus. Ectopic co-expression of Foxi2 and Sox3 in prospective endodermal tissue induces the expression of ectodermal markers while suppressing mesendodermal markers. Transcriptomics analyses reveal that Foxi2 and Sox3 jointly and independently regulate hundreds of ectodermal target genes. During early cleavage stages, Foxi2 and Sox3 pre-bind to key cis-regulatory modules (CRMs), marking sites that later recruit Ep300 and facilitate H3K27ac deposition, thereby shaping the epigenetic landscape of the ectodermal genome. These CRMs are highly enriched within ectoderm-specific super-enhancers (SEs). Our findings highlight the pivotal role of ectodermal SE-associated CRMs in precise and robust ectodermal gene activation, establishing Foxi2 and Sox3 as central architects of ectodermal lineage specification.

Ep300↗
PubMed2025

Foxi2 and Sox3 are master transcription regulators that control ectoderm germ layer specification in Xenopus.

Germ layer specification represents a critical transition where pluripotent cells acquire lineage-specific identities. We identify the maternal transcription factors Foxi2 and Sox3 to be pivotal master regulators of ectodermal germ layer specification in Xenopus. Ectopic co-expression of Foxi2 and Sox3 in prospective endodermal tissue induces the expression of ectodermal markers while suppressing mesendodermal markers. Transcriptomic analyses reveal that Foxi2 and Sox3 jointly and independently regulate hundreds of ectodermal target genes. During early cleavage stages, Foxi2 and Sox3 pre-bind to key cis-regulatory modules (CRMs), marking sites that later recruit Ep300 and facilitate H3K27ac deposition, thereby shaping the epigenetic landscape of the ectodermal genome. These CRMs are highly enriched within ectoderm-specific super-enhancers (SEs). Our findings highlight the pivotal role of ectodermal SE-associated CRMs in precise and robust ectodermal gene activation, establishing Foxi2 and Sox3 as central architects of ectodermal lineage specification.

Animals↗
PubMed1985

Sequential expression of germ-layer specific molecules in the sea urchin embryo.

Described are two germ-layer specific molecules that appear coincident with the formation of two germ layer cell lineages in the sea urchin embryo. Meso1 is a molecule of 380 kDa that is first detected at the time of primary mesenchyme cell delamination from the wall of the blastula. Endo1 is a molecule of 320 kDa that appears on endoderm cells at the time of archenteron formation a few hours after Meso1 appears. Both antigens are identified by monoclonal antibodies. The appearance of these antigens is described by immunofluorescence microscopy, and quantitative data on their localization has been obtained by ultrastructural immunoelectron microscopy. The synthesis of the molecules has been followed by pulse-chase immunoprecipitation. Meso1 is first expressed in trans Golgi-like saccules, is concentrated in peripheral low electron-dense vesicles, and is found throughout the plasma membrane of the mesenchymal cells and their filopodial extensions. Newly translated Meso1 can first be immunoprecipitated upon differentiation of the mesoderm cell lineage, and pulse-chase studies suggest that the determinant is the result of a post-translational modification. [35S]Methionine pulses early in development followed by a chase to the mesenchyme blastula or prism stage show that at least a portion of the molecule is translated well in advance of the mesenchyme blastula stage. Endo1, in contrast, does not appear to be translated until the onset of gastrulation, just preceding the post-translational expression of the Endo1 determinant. Endo1 is localized to the apical and basolateral cell surfaces of the midgut and hindgut. No label is detected in foregut cells, demonstrating a heterogeneity of cell populations within the endoderm cell lineage corresponding to a difference in morphology. In addition, Endo1 is shown to be the result of new transcription by the embryonic genome. Even though the function of neither molecule is known, together they show the spatial and temporal precision of differentiation that accompanies the formation of germ layers.

Animals↗
PubMed1991

Development of separated germ layers of rodent embryos on ectopic sites: a reappraisal.

The method of separation of germ layers of rodent embryos by treating the embryonic shields with proteolytic enzymes and by microsurgery with the subsequent transplantation to ectopic sites has helped to gain a more detailed insight into what is going on during gastrulation in mammals. The space under the kidney capsule of adult animals seems to be the most appropriate ectopic site for transplantation of early postimplantation rat embryos or separated germ layers. After transplantation the grafts develop into teratomas whose complex histological structure reflects the initial developmental capacities of the graft. At the pre-primitive streak and the early primitive streak stages the primitive ectoderm differentiates into tissue derivatives of all three definitive germ layers, often in complex organotypic combinations. This is indirect evidence that all cells of the embryonic body originate from the primitive embryonic ectoderm. Halves of the primitive ectoderm obtained by a longitudinal or transverse cut through the egg cylinder give the same result. At the head fold stage the capacity for differentiation of the ectoderm is restricted to ectodermal and mesodermal derivatives. One day before gastrulation the isolated primitive ectoderm is not able to differentiate as renal isograft. The mesoderm isolated at the head fold stage and at later stages when its segmentation occurs, differentiates almost exclusively into the brown adipose tissue. The embryonic endoderm differentiates only in combination with the mesoderm. After transplantation the embryonic ectoderm loses its epithelial organization and breaks up into a mass of mesenchyme-like cells in which epithelial structures subsequently appear and differentiate in a way reminiscent of the reaggregation of cells in mixed cell suspension in vitro.

Animals↗
PubMed1992

Establishment and organization of germ layers in the gastrulating mouse embryo.

By following the distribution of wheat germ agglutinin-gold-labelled cells in primitive streak stage embryos, we obtained direct evidence for a continuous recruitment of the embryonic ectoderm cells to the definitive endoderm and to the embryonic and extraembryonic mesoderm during gastrulation. The majority of the definitive endodermal cells ingressed through the anterior end of the primitive streak and were incorporated initially into the midline endoderm at the archenteron, but a small population of endodermal cells may be recruited by direct delamination from the embryonic ectoderm. The pre-existing visceral embryonic endoderm was progressively replaced, but not totally, by the newly recruited population which colonized the embryonic foregut and the notochord. The developmental fate of the recruited endoderm and that of cells in the embryonic ectoderm and the mesoderm of late primitive streak stage embryos indicate that concomitant with the establishment of the germ layers, an orderly allocation of prospective fetal tissues to specific parts of the body occurs simultaneously in all three germ layers.

Animals↗
PubMed1992

Embryonal germ-layer antigens: target for autoimmunity.

Histopathological analysis of some systemic autoimmune diseases and syndromes led us to the conclusion that the common feature of the organs involved might be their embryonal origin. We suggest that organs derived from the same germ layer express common germ-layer-specific antigens. Such antigens could serve as target antigens for the autoimmune response.

Autoantibodies↗
PubMed1990

Induction across germ layers in Drosophila mediated by a genetic cascade.

We report an induction process occurring between two germ layers in the Drosophila embryo that involves a cascade of five interacting genes. Two of these, Ultrabithorax and abdominal-A, encode nuclear homeobox proteins; each of them is expressed in one of two adjacent parasegments in the visceral mesoderm and directs expression in its parasegment of a separate target gene, decapentaplegic in parasegment 7 and wingless in parasegment 8. The activity of both target genes is required for normal expression of another homeotic gene, labial, in cells of the adhering midgut epithelium. Their products are putative extracellular proteins, which presumably act as signals between the two germ layers. Positional instruction of this kind may be needed since the endoderm, unlike the mesoderm, appears unsegmented at first as it originates from two primordia near the embryonic poles, outside the realm of segmentation genes.

Animals↗
PubMed1992

The germ layer origin of mouse vaginal epithelium restricts its responsiveness to mesenchymal inductors: uterine induction.

The epithelium of the mammalian vagina arises from two distinct germ layers, endoderm from the urogenital sinus and mesoderm from the lower fused Müllerian ducts. While previously it has been reported that neonatal vaginal epithelium can be induced to differentiate as uterus, which normally develops from the middle portion of the Müllerian ducts, it has not been determined whether this ability is shared by both mesoderm- and endoderm-derived vaginal epithelia. To test if germ layer origin influences the ability of vaginal epithelium to undergo uterine differentiation, we have isolated sinus-derived and Müllerian-derived vaginal epithelia from newborn mice, combined them with uterine mesenchyme, and grown them for 4 weeks in female mice. Mesoderm-derived Müllerian vaginal epithelium in combination with uterine mesenchyme formed the simple columnar epithelium typical of uterus. Similar results were obtained with neonatal cervical epithelium, another mesodermal Müllerian duct derivative. On the other hand, sinus vaginal epithelium combined with uterine mesenchyme formed small cysts lined by a stratified squamous vaginal-like epithelium. This epithelium never showed evidence of cycling between the cornified and mucified states as is typically seen in vaginal epithelium combined with vaginal stroma. These results indicate that the ability of epithelium to form uterus is limited to mesoderm-derived epithelia and suggest that endoderm-derived sinus vaginal epithelium cannot undergo the typical differentiative modifications in response to the hormonal fluctuations of the estrous cycle when associated with uterine stroma.

Animals↗
PubMed1991

Clonal analysis of epiblast fate during germ layer formation in the mouse embryo.

The fate of cells in the epiblast at prestreak and early primitive streak stages has been studied by injecting horseradish peroxidase (HRP) into single cells in situ of 6.7-day mouse embryos and identifying the labelled descendants at midstreak to neural plate stages after one day of culture. Ectoderm was composed of descendants of epiblast progenitors that had been located in the embryonic axis anterior to the primitive streak. Embryonic mesoderm was derived from all areas of the epiblast except the distal tip and the adjacent region anterior to it: the most anterior mesoderm cells originated posteriorly, traversing the primitive streak early; labelled cells in the posterior part of the streak at the neural plate stage were derived from extreme anterior axial and paraxial epiblast progenitors; head process cells were derived from epiblast at or near the anterior end of the primitive streak. Endoderm descendants were most frequently derived from a region that included, but extended beyond, the region producing the head process: descendants of epiblast were present in endoderm by the midstreak stage, as well as at later stages. Yolk sac and amnion mesoderm developed from posterolateral and posterior epiblast. The resulting fate map is essentially the same as those of the chick and urodele and indicates that, despite geometrical differences, topological fate relationships are conserved among these vertebrates. Clonal descendants were not necessarily confined to a single germ layer or to extraembryonic mesoderm, indicating that these lineages are not separated at the beginning of gastrulation. The embryonic axis lengthened up to the neural plate stage by (1) elongation of the primitive streak through progressive incorporation of the expanding lateral and initially more anterior regions of epiblast and, (2) expansion of the region of epiblast immediately cranial to the anterior end of the primitive streak. The population doubling time of labelled cells was 7.5 h; a calculated 43% were in, or had completed, a 4th cell cycle, and no statistically significant regional differences in the number of descendants were found. This clonal analysis also showed that (1) growth in the epiblast was noncoherent and in most regions anisotropic and directed towards the primitive streak and (2) the midline did not act as a barrier to clonal spread, either in the epiblast in the anterior half of the axis or in the primitive streak. These results taken together with the fate map indicate that, while individual cells in the epiblast sheet behave independently with respect to their neighbours, morphogenetic movement during germ layer formation is coordinated in the population as a whole.

Animals↗
PubMed1991

The response of female urogenital tract epithelia to mesenchymal inductors is restricted by the germ layer origin of the epithelium: prostatic inductions.

The epithelium of the mammalian vagina arises from two distinct germ layers, endoderm from the urogenital sinus and mesoderm from the Müllerian ducts. While neonatal vaginal epithelium can be induced to form prostate which is normally an endodermal derivative, it has not been determined whether this ability to form prostate is shared by both mesoderm- and endoderm-derived vaginal epithelia. To test the competence of vaginal epithelia we have isolated sinus-derived and Müllerian-derived vaginal epithelia from newborn mice, combined them with rat urogenital sinus mesenchyme, and grown the tissue recombinants for 4 weeks in male athymic nude mice. Endoderm-derived sinus vaginal epithelium was induced to form prostatic tissue which expressed prostate-specific secretory proteins in 21 of 23 tissue recombinants. Müllerian-derived vaginal epithelium formed small ducts and cysts lined by a simple epithelium. These latter tissue recombinants lacked any evidence of prostatic secretory proteins. Similarly, endoderm-derived urethral epithelium was induced to form prostate (17 of 17 cases), while mesoderm-derived uterine epithelium was not (0 of 13 cases). Therefore, the ability to form prostatic epithelium was limited to endodermal derivatives of the urogenital tract.

Androgen-Binding Protein↗
PubMed2025

Glycolytic activity instructs germ layer proportions through regulation of Nodal and Wnt signaling.

Metabolic pathways can influence cell fate decisions, yet their regulative role during embryonic development remains poorly understood. Here, we demonstrate an instructive role of glycolytic activity in regulating signaling pathways involved in mesoderm and endoderm specification. Using a mouse embryonic stem cell (mESC)-based in vitro model for gastrulation, we found that glycolysis inhibition increases ectodermal cell fates at the expense of mesodermal and endodermal lineages. We demonstrate that this relationship is dose dependent, enabling metabolic control of germ layer proportions through exogenous glucose levels. We further show that glycolysis acts as an upstream regulator of Nodal and Wnt signaling and that its influence on cell fate specification can be decoupled from its effects on growth. Finally, we confirm the generality of our findings using a human gastrulation model. Our work underscores the dependence of signaling pathways on metabolic conditions and provides mechanistic insight into the nutritional regulation of cell fate decision-making.

Glycolysis↗
PubMed1991

The snail gene required for mesoderm formation in Drosophila is expressed dynamically in derivatives of all three germ layers.

The zygotic effect gene snail (sna) encodes a zinc-finger protein required for mesoderm formation in Drosophila embryos. By in situ analysis, sna transcripts are first detected at syncytial blastoderm and persist until very late stages of embryogenesis. Expression of sna is transient and is observed in tissues derived from all three germ layers. Prior to germband elongation, sna RNA accumulation is consistent with its genetically determined role in mesoderm formation. Starting at germband elongation, a second phase of sna expression appears to be initiated, characterized by a highly dynamic accumulation of transcripts in the developing central and peripheral nervous systems. Translation of sna RNA is apparently delayed as the sna protein is not detected before the onset of gastrulation. Its regional distribution generally correlates with that of sna transcripts. The complex pattern of sna expression strongly suggests that the function of the gene is not restricted to mesoderm formation.

Animals↗
PubMed1979

Fine structural differentiation of germ layers in the mouse at the time of mesoderm formation.

The morphology of early postimplantation mouse egg cylinders was studied using light and electron microscopy. Implantation sites at seven, seven and one-half and eight days of gestation were dissected from the myometrium and whole implants, including both decidua and egg cylinders were processed for electron microscopy. Pre-primitive streak egg cylinders were composed of two germ layers, a tall columnar ectoderm and an outer visceral endodermal layer. Ectodermal cells demonstrated large oval nuclei and an organelle sparse cytoplasm except for many free polyribosomes. The visceral endodermal layer was composed of two cell populations. One visceral endodermal cell type observed was tall columnar in shape and appeared absorptive as demonstrated by many microvilli, pinocytotic profiles and lysosomal granules. This population was confined to extraembryonic regions of the egg cylinder. The second visceral endodermal cell type, squamous in shape, evidenced only a few microvilli, pinocytotic profiles and lysosomal granules. This population was confined to the embryonic region of the egg cylinder. Concurrent with the formation of the primitive streak an increased number of cellular junctions and nuclear pores became evident in the ectoderm. Mesodermal cells were large and stellate-shaped exhibiting many filapodia which made contact with adjacent mesodermal elements. Later the cephalic region of the primitive streak proliferated resulting in the migration of wedge-shaped mass of cells, the head process. At the most ventral extremity of the post-primitive streak egg cylinder the cells of the head process became intimately associated with the ectoderm by areas of focal contact and gap junctions.

Animals↗
PubMed1990

A Drosophila growth factor homolog, decapentaplegic, regulates homeotic gene expression within and across germ layers during midgut morphogenesis.

The decapentaplegic (dpp) gene product, a member of the transforming growth factor-beta family, is required in Drosophila embryos for normal gastrulation and the establishment of dorsal-ventral polarity in the embryo. dpp is also expressed at specific positions in the visceral mesoderm along the developing midgut. We find that mutations that eliminate the visceral mesoderm expression of dpp lead to defects in midgut morphogenesis and alter the spatially localized expression of the homeotic genes Sex combs reduced (Scr), Ultrabithorax (Ubx), and Antennapedia (Antp) in the visceral mesoderm. The extracellular dpp protein migrates from the visceral mesoderm across the apposing endodermal cell layer in a region of the endoderm that expresses the homeotic gene labial (lab). Mesodermal expression of dpp is required for the expression of lab in these endodermal cells indicating that dpp mediates an inductive interaction between the two germ layers. We propose that extracellular dpp protein regulates gut morphogenesis, in part, by regulating homeotic gene expression in the visceral mesoderm and endoderm of the developing midgut.

Animals↗
PubMed1992

The vertebrate tail bud: three germ layers from one tissue.

The tail bud of amniote embryos comprises a mass of apparently undifferentiated mesenchymal cells located at the caudal limit of the embryo, representing the remains of Hensen's node and the primitive streak. These cells have the potential to give rise to a variety of different tissues including the posterior or 'secondary' neural tube, the tail gut, and somites and their derivatives. This seemingly homogeneous accumulation of cells therefore has the capacity to differentiate into tissues which in more cranial regions of the embryo are derived from cells of different germ layers. In this review, the tissue contributions of the tail bud in various vertebrate classes are discussed, with particular attention to the mesenchymal-to-epithelial transformation that characterizes the process of secondary neurulation, and which distinguishes it from the epithelial folding that occurs during primary neurulation in more cranial regions. Recent studies suggest that the transformation is accompanied by extensive changes in the cell surface oligosaccharide complement of the differentiating cells, and that the sialyted form of N-CAM is expressed both temporally and spatially in a manner that suggests a role for it in the process. The pluripotential nature of the tail bud mesenchyme may be revealed experimentally by grafting the tissue ectopically, or by culturing it on different substrata. In the latter case, the mesenchyme can be demonstrated to give rise to myocytes, chondrocytes, neuroepithelium and neural crest derivatives such as melanocytes, depending on the nature of the culture substratum. It is concluded that the tail bud mesenchyme represents a developing system which is readily amenable to experimentation and should provide insights into the general mechanisms of cell differentiation and transformation.

Amphibians↗