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PubMed1995

Alteration of Ca2+ homeostasis of sea urchin embryos by retinoid CD 367, dual effect on egg cleavage and embryonic development.

The effect of a light stable retinoid (CD 367) was studied on sea urchin embryos. CD 367 did not affect sperm-egg interaction. In a range of concentrations between 10 and 100 microM, CD 367 delayed the first and the second cleavages. When added after fertilization, micromolar amounts of CD 367 delayed hatching and produced embryonic abnormalities in a dose-dependent manner. Mesodermal cells, primary (PMC) and secondary (SMC) mesenchyme cells migration was particularly disturbed, leading to exogastrulations and calcified spicules malformations. Concentrations of CD 367 higher than 8 microM were embryolethal. Micromolar amount of CD 367 increased plasmalemma Ca2+ permeability of fertilized eggs but not of unfertilized eggs. CD 367 inhibited ATP-dependent intracellular sequestration of Ca2+ in a range of concentrations similar to those affecting egg cleavage and embryonic structures. Since we were unable to detect nuclear receptors for CD 367 in sea urchin eggs and ovocytes, these effects probably are not related to interaction of the retinoid with members of the RAR family, to which CD 367 has a high affinity, but rather to its toxicity by the means of some unknown mechanisms.

Animals↗

PubMed2004

Cooperative activation of atrial naturetic peptide promoter by dHAND and MEF2C.

An intricate array of cell-specific multiprotein complexes participate in programs of cell-specific gene expression through combinatorial interaction with different transcription factors and cofactors. The dHAND basic helix-loop-helix (bHLH) transcription factor, which is essential for heart development and extra embryonic structures, is thought to regulate cardiomyocyte-specific gene expression through combinatorial interactions with other cardiac-restricted transcription factors such as GATA4 and NKX2.5. Here, we determine that dHAND also interacts with the myocyte enhancer binding factor-2c (MEF2C) protein, which belongs to MADS-box transcription factors and is essential for heart development. dHAND and MEF2C synergistically activated expression of the atrial naturetic peptide gene (ANP) in transfected HeLa cells. GST-pulldown and immunoprecipitation assay demonstrate that full-length MEF2C protein is able to interact with dHAND in vitro and in vivo, just like MEF2A and bHLH transcription factors MyoD in skeletal muscle cells. In addition, electrophoretic mobility shift assays (EMSAs) demonstrate that MEF2C and dHAND do not influence each other's DNA binding activity. Using chromatin immunoprecipitation (ChIP) analysis in H9c2 cells we show that dHAND interact with MEF2C to form protein complex and bind A/T sequence in promoter of ANP. Taken together with previous observations, these results suggest the existence of large multiprotein transcriptional complex with core DNA binding proteins that physically interact with other transcriptional factors to form favorable conformation to potentiate transcription.

Atrial Natriuretic Factor↗

PubMed2002

Inflamed urachal cyst containing calculi in an adult.

The urachus is an embryonic structure that persists after birth in some individuals and can cause various problems. We report a case of an inflamed urachal cyst filled with a thick yellow fluid and several calculi in a woman with a 1-month history of dysuria. Physical examination revealed a fist-sized tumor located infraumbically in the midline. The patient's erythrocyte sedimentation rate was elevated; the results of all other routine laboratory studies were normal. Sonography showed a regularly shaped, ovoid, hypoechoic cystic area in the abdominal wall measuring 8 x 4 x 3 cm and containing several hyperechoic masses associated with acoustic shadowing. The wall of the cyst was inhomogeneous, and a thin hypoechoic linear tract linked the superior aspect of the mass to the umbilicus. The results of excretory urography, voiding cystography, and cystoscopy excluded an abnormality of the urinary system. A urachal cyst was diagnosed, and the mass was surgically removed. The surgical specimen was sent for histopathologic analysis, which confirmed the diagnosis.

Aged↗

PubMed1982

Development of early somitic mouse embryos in static culture in vitro.

We have compared the in vitro development of 8.5-day early somitic mouse embryos cultured in static organ cultures dishes in human cord serum or rat serum with the development of embryos of the same age cultured in rotating tubes or developing in vivo. The growth of embryos cultured in rat serum in organ culture dishes was comparable during the first 24 hours, with the growth achieved in rotating tubes and paralleled the embryonic growth in vivo. The morphogenesis of embryos in static organ culture was delayed in comparison with the normal embryogenesis in vivo, but was not statistically different from embryos developing in rotating tube cultures. Embryos cultured for 36 hours continued to grow but were almost all lagging in development behind the embryos developing in utero or in the rotating tubes. Our data show that 24-hour culture of somitic mouse embryos in rat serum may be used to evaluate the growth of explanted embryos, and to study the in vitro development and function of certain embryonic structures, such as somite number, yolk sac circulation, heart function, and development of allantois. Static culture is inadequate for the study or evaluation of neural fold closure, branchial arch formation, anterior limb bud formation, and axial turning of the explanted embryos. Embryo cultures in rat serum yield better results than do cultures in human cord serum.

Animals↗

PubMed1979

Equivalent ages in rat, mouse and chick embryos.

Data for estimating equivalent ages of rat, mouse and chick embryos are presented, using several sources from the literature. When the time of development of various embryonic structures is matched for the three species, the differences in time for the stages are primarily due to delays in development of the preimplantation blastulas of the rat and mouse in comparison with the incubated chick egg. Development from the blastula stage to completion of major organogenesis proceeds at approximately the same rate for all three species.

Animals↗

PubMed1989

Difference in teratogenic potency of ethylenethiourea in rats and mice: relative contribution of embryonic and maternal factors.

Ethylenethiourea (ETU) is a potent teratogen in the rat but not in the mouse or any other species tested. Embryotoxic and teratogenic effects are produced in mice only after exposure to 10-40 times the teratogenic dose of ETU in rats. This study was undertaken to determine whether the difference in sensitivity between rats and mice is due to differences within the embryo, to maternal metabolic differences, or both. Comparably staged rat and mouse embryos (gestation day 10.5 and 8.5, respectively) with intact extra-embryonic membranes were maintained under identical conditions in whole embryo culture and exposed to static concentrations of ETU for 48 hours. The teratogenic effects of ETU were qualitatively similar in both species, characterized by excessive fluid accumulations in embryonic structures. The most common abnormalities were distended neural tube, especially in the hindbrain, and clear blisters on the caudal region. At least two times as much ETU was required to produce a similar incidence of abnormalities in mice as in rats. Thus, there is some intrinsic difference in the quantitative response of rat and mouse embryos to ETU, but it is insufficient to account for the in vivo discrepancy. The role of maternal metabolism in modifying the teratogenicity of ETU was assessed by adding hepatic S-9 fractions from Aroclor 1254-induced rats and mice to whole embryo culture. Rat S-9 had no effect on ETU teratogenicity. Mouse S-9 virtually eliminated the formation of abnormalities typical of ETU in both rat and mouse embryos. Decreased exocoelomic fluid osmolality, a physiological effect produced by ETU, also was not observed in embryos exposed to ETU and mouse S-9. ETU-typical defects were observed in embryos exposed to ETU and mouse S-9 which had been treated with carbon monoxide to inactivate its monooxygenase system, indicating that the mouse S-9 was metabolizing ETU. A surprising result was that adding mouse S-9 to embryo cultures containing ETU resulted in the formation of abnormalities (principally open neural tube) that were not observed in in vitro rat or mouse embryos exposed to ETU alone, or in mouse embryos in vivo. We believe that the most likely cause of these abnormalities is a putative ETU metabolite, which is rapidly excreted by the dam in vivo, but accumulates to teratogenic concentrations in vitro.

Animals↗

PubMed1994

Localization of transcription factor GATA-4 to regions of the mouse embryo involved in cardiac development.

To clarify the role of transcription factor GATA-4 in mammalian development, we have determined the pattern of expression of GATA-4 in early postimplantation mouse embryos. Using in situ hybridization and immunohistochemistry, we find that GATA-4 RNA and protein are expressed in cells associated with heart development. Intraembryonic expression of GATA-4 RNA is first apparent in coelomic epithelial cells of the primitive streak embryo (approximately 7.0-7.5 days postcoitum). During formation and bending of the heart tube (approximately 8 days postcoitum), GATA-4 RNA and protein are expressed in endocardium, myocardium, and embryonic structures containing precardiac mesoderm such as the septum transversum and intraembryonic coelomic epithelium. By the onset of cardiac septation (approximately 9 days postcoitum), abundant GATA-4 RNA expression is evident in endocardium, endocardial cushion tissue, and myocardium. Expression of GATA-4 by the myocardium continues through gestation and after birth. The temporal and spacial patterns of GATA-4 expression support a role for this factor in the regulation of cardiac differentiation, analogous to the established role of transcription factor GATA-1 in the regulation of hematopoiesis.

Animals↗

PubMed2000

The zebrafish floating head mutant demonstrates podocytes play an important role in directing glomerular differentiation.

In zebrafish, the pronephric glomerulus occupies a midline position underneath the notochord and is vascularized through angiogenic capillary ingrowth from the dorsal aorta. The midline mutants floating head (flh), sonic you (syu), and you-too (yot) provide the opportunity to study glomerular differentiation in the absence of the notochord and vascularization from the dorsal aorta. In flh, syu, and yot mutants, glomeruli differentiate at ectopic lateral positions within the embryo and contain morphologically identifiable podocyte and endothelial cell types. In the absence of the dorsal aorta, endothelia from an alternate source are recruited by podocytes during glomerular vascularization to make functional glomeruli. Our results suggest that midline signals are required for proper glomerular morphogenesis but not for the differentiation of podocytes. Podocytes appear to play an important role in directing cellular recruitment events leading to glomerular differentiation. Furthermore, we find defects in sclerotomal development that correlate with defects in glomerular morphogenesis suggesting a possible link between the formation of these embryonic structures.

Animals↗

PubMed2001

The whereabouts of a morphogen: direct evidence for short- and graded long-range activity of hedgehog signaling peptides.

Sonic Hedgehog (Shh) and Indian Hedgehog (Ihh) are members of the Hedgehog (Hh) family of signaling molecules known to be involved in embryonic patterning and morphogenesis. The Hh proteins undergo an autocatalytic cleavage to yield an N-terminal and a C-terminal peptide, with the signaling capacities confined to the N peptide. Drosophila Hh-N has been shown to act via both short- and long-range signaling. In vertebrates, however, attempts to directly demonstrate Shh (SHH) or Ihh (IHH) proteins at a distance from producing cells have been largely unsuccessful. Furthermore, the fact that the Hh N peptides occur in a cholesterol-modified, membrane-tethered form is not easily reconciled with long-range signaling. This study used optimized immunohistochemistry combined with tissue separation and biochemical analyses in vivo and in vitro to determine the range of action of SHH and IHH in the mouse embryo. In all embryonic structures studied, we detect signaling peptides in producing cells, but we also find that ligands move over considerable distances depending on the tissue. These data provide direct evidence for the presence of Hedgehog signaling peptides in target compartments, suggesting a direct long-range action without a need for secondary mediators. Visualization of Hedgehog proteins in target tissues was achieved only under conditions that allowed proteoglycan/glycosaminoglycan (PG/GAG) preservation. Furthermore, we show that induced changes of the composition of PG/GAG in the tooth alter SHH signaling. These data suggest a crucial role for PG/GAGs in Hedgehog movement.

Animals↗

PubMed2001

Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function.

The secreted protein encoded by the Sonic hedgehog (Shh) gene is localized to the posterior margin of vertebrate limb buds and is thought to be a key signal in establishing anterior-posterior limb polarity. In the Shh(-/-) mutant mouse, the development of many embryonic structures, including the limb, is severely compromised. In this study, we report the analysis of Shh(-/-) mutant limbs in detail. Each mutant embryo has four limbs with recognizable humerus/femur bones that have anterior-posterior polarity. Distal to the elbow/knee joints, skeletal elements representing the zeugopod form but lack identifiable anterior-posterior polarity. Therefore, Shh specifically becomes necessary for normal limb development at or just distal to the stylopod/zeugopod junction (elbow/knee joints) during mouse limb development. The forelimb autopod is represented by a single distal cartilage element, while the hindlimb autopod is invariably composed of a single digit with well-formed interphalangeal joints and a dorsal nail bed at the terminal phalanx. Analysis of GDF5 and Hoxd11-13 expression in the hindlimb autopod suggests that the forming digit has a digit-one identity. This finding is corroborated by the formation of only two phalangeal elements which are unique to digit one on the foot. The apical ectodermal ridge (AER) is induced in the Shh(-/-) mutant buds with relatively normal morphology. We report that the architecture of the Shh(-/-) AER is gradually disrupted over developmental time in parallel with a reduction of Fgf8 expression in the ridge. Concomitantly, abnormal cell death in the Shh(-/-) limb bud occurs in the anterior mesenchyme of both fore- and hindlimb. It is notable that the AER changes and mesodermal cell death occur earlier in the Shh(-/-) forelimb than the hindlimb bud. This provides an explanation for the hindlimb-specific competence to form autopodial structures in the mutant. Finally, unlike the wild-type mouse limb bud, the Shh(-/-) mutant posterior limb bud mesoderm does not cause digit duplications when grafted to the anterior border of chick limb buds, and therefore lacks polarizing activity. We propose that a prepattern exists in the limb field for the three axes of the emerging limb bud as well as specific limb skeletal elements. According to this model, the limb bud signaling centers, including the zone of polarizing activity (ZPA) acting through Shh, are required to elaborate upon the axial information provided by the native limb field prepattern.

Animals↗

PubMed1989

Heparitinase treatment of rat embryos during cranial neurulation.

Heparan sulphate has been reported to be present in rat embryos. It is covalently linked to a core protein as heparan sulphate proteoglycan (HSPG). Heparitinase specifically degrades heparan sulphate, thus treatment of rat embryos with this enzyme in vitro should result in the perturbation of any tissue interactions which involve heparan sulphate proteoglycan. In this study heparitinase was either added to the culture medium or microinjected directly into the amniotic cavity. Heparitinase treatment resulted in abnormal development of the whole embryo, but the earliest effects were observed in the cranial region. Forebrain development was grossly abnormal: the neural folds remained widely open, with beak-like outgrowths rostrally. Optic sulci failed to develop. The midbrain and rostral hindbrain neural folds also remained widely open. In the trunk, where the pattern of neurulation is less complex than in the cranial region, rostral neural tube closure did occur although the morphology of the closed region was far from normal. These results suggest that heparan sulphate proteoglycan is essential for normal neurulation. Epithelial somite formation was perturbed, but neural crest cell emigration, otic pit formation and pharyngeal arch formation, all important morphogenetic events which occur during this period of development, were not inhibited by heparitinase treatment. Prolonged (44 h) exposure to the enzyme resulted in the conversion of the embryonic structure to a much simpler form: mesenchymal cells (stellate or spindle-shaped) enclosed within a simple epithelial coating.

Animals↗

PubMed1988

Heart anatomy and developmental biology.

The subject of heart development has attracted the interest of many embryologists over the last two centuries. As a result, the main morphologic features of the developmental anatomy of the heart are already well established. Although there are still some controversial points, and there is probably much descriptive work yet to be done, emphasis is currently being placed on developmental mechanisms rather than simply on descriptive facts. The availability of new techniques and the overall advances in biological research are placing heart embryology in a new perspective. Today, we do not simply ask whether one or another embryonic structure arises further right or further left; instead, we are studying how cells, tissues, and their microenvironment interrelate at the several levels of biological organization (from the gene upwards) so as to give rise to a mature organ with a distinct shape and well-established functions. This paper attempts to review some of the basic aspects of the developmental anatomy of the heart. Descriptive embryology is used here as a tool. Emphasis is placed on developmental mechanisms, and on the present knowledge of how these mechanisms are related to the structural development of the heart.

Animals↗

PubMed1989

[Psychosomatic problems of childless couples].

We discuss the late "wish for pregnancy" (involving women over 45 years of age). Late hopes for in vitro fertilization occur, encouraged by "solutions" that are deceptive and to our experience distract from inner conflicts. We consider the problems of idiopathic infertility, a diagnosis that is frequently accepted as final without exploration of the psychological background. Finally, we discuss secondary sexual dysfunctions, caused by a very technical approach to infertility treatment. We conclude with a demand for critical discussion of neuralgic problems in modern reproductive medicine (e.g., manipulation of embryonic structures and breaking up of family structures).

Female↗

PubMed2000

Double-layered manubrium sterni in young children with diastrophic dysplasia.

A review of the roentgenograms, which included a lateral view of the sternum in 12 children with diastrophic dysplasia, revealed that 4 children (2 newborns, and 2 aged 1.5 years) had a double-layered manubrium with the accessory ossification located ventral to the normal manubrium. In the other 2 children, aged 5 and 11.5 years, the manubrium showed a deformity consistent with a previous double-layered manubrium in which the ventral ossification had fused with the normal dorsal element. The nature of this anomaly is not certain, but a survey of the embryology of the manubrium raises the possibility of a persistence and ossification of a primitive midline embryonic structure that normally is resorbed in its cartilaginous state.

Child↗

PubMed2006

Entrapment of pacemaker lead by a large net-like Eustachian valve within the right atrium.

During pacemaker implantation in a patient with permanent atrial fibrillation, it remained impossible to advance a passive fixation lead with fins through the right atrium. However, a lead with a retractable screw easily passed the right atrium and was positioned in the right ventricle. Transesophageal echocardiography revealed an extensive net-like perforated Eustachian valve within the right atrium that had caused entrapment of the anchor fins during lead implantation. Remnants of embryonal structures within the right atrium should be considered a rare possible barrier during pacemaker implantation.

Aged↗

PubMed1997

The Eph family: a multitude of receptors that mediate cell recognition signals.

The Eph receptor tyrosine kinases are emerging as molecules that guide the migration of cells and growth cones during embryonic development. Based on their concentration in embryonic regions containing growing neuronal processes, the Eph receptors were suspected early on to have a role in regulating aspects of axon growth. The most distinctive role of the Eph receptors appears to be their ability to mediate cell-cell repulsion through the binding of a ligand on an adjacent cell surface. The repulsive interactions are presumably mediated by transient receptor activation at the boundaries of complementary regions of high ligand or receptor expression. In contrast, overlapping expression patterns may regulate cell adhesion and cytoskeletal organization with possible consequences on the overall growth and fasciculation of neuronal processes. A notable feature of Eph receptor signaling is that, upon receptor binding, responses may also be elicited in the ligand-expressing cells. A better understanding of Eph receptor function requires the elucidation of their signaling properties. Recent evidence suggests a functional interaction between the Eph receptor EphB2 and neural cell adhesion molecules of the L1 family, which have well-recognized roles in the formation of neuronal projections. Only a few cytoplasmic signaling molecules that bind to the activated Eph receptors have been identified. Several of these molecules are known to transduce signals regulating cytoskeletal organization and neurite outgrowth. It is currently unclear why there is a need for fourteen distinct Eph receptor genes, many of which appear to encode several variant forms with distinct functional properties, but it is tempting to speculate that such diversity is necessary to refine the spatial organization of embryonic structures.

Animals↗

PubMed2002

Laparoscopic resection of patent omphalomesenteric duct in an adult.

The omphalomesenteric duct is the embryonic structure connecting the yolk sac to the primitive gut that disappears at 8 to 9 weeks of gestation. Failure of this duct to involute results in various anomalies. Failure of complete closure at different stages results in various anomalies, which occur in approximately 2% of the population. However, complete patency of omphalomesenteric duct is rare, reportedly occurring in approximately 15% omphalomesenteric duct anomalies. Adult presentations are extremely rare. We report the case of a 44-year-old man with a patent omphalomesenteric duct (POMD). He was admitted with a foul-smelling discharge from the umbilicus that he had experienced for 5 years. The condition had been interpreted as an umbilical granuloma at other centers, and multiple unsuccessful sessions of cauterization with silver-nitrate bar had been performed. At laparoscopy through three ports, the POMD was resected with the aid of a laparoscopic linear stapler. To our knowledge, this is the first adult case of POMD resected laparoscopically. The pitfalls of this diagnosis in the adult and the technique of laparoscopic resection is discussed in light of the available literature.

Adult↗

PubMedDate not supplied

Intraoral tumor of Chievitz in a child.

Juxtaoral organs known as organs of Chievitz are intramuscular embryonic structures found close to the angle of the mandible near the insertion of the pterygomandibular raphae. They are considered of neuroepithelial origin with no known function. We describe the first tumor of the organ of Chievitz which presented intraorally in a child. Immunohistochemically, the Chievitz nests showed positive reaction for vimentin, cytokeratins, and epithelial membrane antigen and ultrastructurally demonstrated cytoplasmic processes and intermediate filament bundles. These observations, together with light microscopic features, suggest that the epithelial nests of the organ of Chievitz are meningothelial rather than neuroepithelial.

Antigens, Neoplasm↗