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PubMed1976

The use of 'normal' and 'transformed' gynandromorphs in mapping the primordial germ cells and the gonadal mesoderm in Drosophila.

The primordial germ cells and the gonadal mesoderm were mapped in the Drosophila embryo by analyzing the patterns of mosaicism in 'normal' and 'transformed' gynandromorphs. Relative to the adult cuticular markers the germ cells map as the posterior most structure, which coincides with their known location in the blastoderm embryo. These data support the hypothesis that the gynandromorph map reflects the real position of the primordia in the embryo. Since after the blastoderm stage the primordial germ cells migrate anteriorly these data also indicate that the map in fact corresponds to the blastoderm stage and not to a later stage of development. The genital disc maps at a single median primordium anterior and ventral to the germ cells, the gonadal mesoderm is located anterior to the genital disc and also forms a single median primordium on the ventral side of the embryo. The primordia for the genital disc and the gonadal mesoderm are unusually large in size, which presumably reflects some indeterminacy of the cell lineage leading to an 'expansion' of the map.

Animals↗

PubMed1998

X-twi is expressed prior to gastrulation in presumptive neurectodermal and mesodermal cells in dorsalized and ventralized Xenopus laevis embryos.

Early X-twi expression has been now investigated from egg laying to the early neurulation stages in Xenopus embryos, using both in situ hydridization and the more sensitive techniques of RT-PCR. We show that in unfertilized eggs, a decreasing gradient of X-twi transcript distribution is observed from animal to vegetative caps. X-twi RNA can be weakly detected at stages prior to gastrulation, and with increased intensity from stage 8 onwards. At blastula, X-twi transcripts are located towards the animal pole, and as gastrulation begins, they are detected in the developing axial mesoderm and then they accumulate in the sensorial layer of the neurectoderm, the mesodermal layer and in neural crest cells up to late neurula stages. We show, in addition, that in lithium-chloride- and UV-treated Xenopus embryos (that are respectively both "anteriorized/dorsalized" and in "posteriorized/ventralized"), X-twi RNA is detected in cells in similar positions to those that express X-twi in normal embryos. As a whole, our results show that X-twi is expressed even when regionalization of the mesoderm is disturbed and raises the question of a putative function of X-twi prior to gastrulation.

Animals↗

PubMed1998

Cooperative effects of growth factors involved in the induction of hematopoietic mesoderm.

Hematopoietic induction occurs on the ventral side of Xenopus gastrulae and is thought to be triggered by the growth factor bone morphogenetic protein 4 (BMP-4). To characterize this process, we developed a quantitative and sensitive assay for the induction of erythroid cells from totipotent ectoderm of the embryo. When high doses of BMP-4 were used in this explant assay, few erythroid cells were detected. In contrast, large numbers of differentiated erythroid cells were induced when ectoderm was treated with BMP-4 and the mesoderm inducers, activin, or fibroblast growth factor (FGF). Ectopic expression of GATA-1 also induced abundant erythroid cells in ectoderm treated with bFGF. This induction of erythroid cells by GATA-1 was blocked by coexpression with a dominant negative BMP-4 receptor, showing that GATA-1 requires the BMP signaling cascade to function. These results suggest that BMP-4 requires mesoderm induction to generate a program of gene expression, which regulates the specification of hematopoietic mesoderm by GATA factors.

Activins↗

PubMed1990

Cellular and genetic responses to mesoderm induction in Xenopus.

Mesodermal cell differentiation begins in response to an inductive interaction early in frog development. In parallel with the recent finding that certain peptide growth factors can induce mesoderm, early cellular and genetic responses to the induction have been discovered. I review here recent work on these responses, work that aims to understand how cells respond to inducers to form the complex pattern of the vertebrate mesoderm.

Animals↗

PubMed2001

Primary peritoneal mesodermal adenosarcoma: report of a case and review of the literature.

BACKGROUND: Mesodermal (müllerian) adenosarcoma arising from the peritoneum is rare and is thought to arise from pluripotent mesothelial and mesenchymal cells of the pelvic cavity or from endometriotic deposits. CASE: A case of primary peritoneal mesodermal adenosarcoma arising from the omentum is described. A 50-year-old woman presented with sudden abdominal distension. Initial laparotomy revealed a 13-kg mass arising from the omentum, which was determined from frozen and paraffin sections to be serous cystadenofibroma. The tumor recurred within 10 months and weighed 18 kg at a second laparotomy. Histopathology and review of the original tumor established the correct diagnosis of mesodermal adenosarcoma. The patient died from disseminated disease 6 months later. CONCLUSION: Adenosarcomas are difficult to differentiate from adenofibromas or endometriosis histologically because of the presence of large areas of low cellularity and infrequent mitotic figures. In such cases, stromal nuclear atypia and periglandular stromal cuffing are features that are diagnostic of adenosarcoma.

Adenosarcoma↗

PubMed1982

Primary malignant mixed mesodermal tumor of the gallbladder. Report of a case and critical review of diagnostic criteria.

A rare case of primary malignant mixed mesodermal tumor of the gallbladder arising in a 75 year old woman is reported. The previously published cases of similar tumors were reviewed in order to outline the histological features and the histogenesis. In diagnosing a malignant mixed mesodermal tumor of the gallbladder it was imperative that we excluded malignant neoplasms with multiple histological patterns. The diffuse and close intermingling of the epithelial and mesenchymal component ruled out a collision tumor. The high mitotic rate, the typical reticulin pattern and the obviously malignant osteoblasts excluded a spindle cell carcinoma with osseous metaplasia. The authors conclude that this is the first case of malignant mixed mesodermal tumor with evident osteosarcomatous areas, described in the gallbladder.

Aged↗

PubMed1998

Simultaneous occurrence of a supra- and an infratentorial glioma in a patient with Ollier's disease: more evidence for non-mesodermal tumor predisposition in multiple enchondromatosis.

A case is presented in which two neuro-ectodermal tumors, an infra- and a supratentorial glioma, developed in a young man with multiple enchondromatosis of Ollier's disease. This is the third such case of multifocal low-grade glioma in Ollier's disease, suggesting a predisposition for non-mesodermal tumors in Ollier's disease. The related condition of multiple enchondromatosis and hemangiomas (Maffucci's syndrome) is well known for its malignant potential, developing both mesodermal and non-mesodermal tumors. Along with other authors, we support the concept of two variants of the same disease with a predisposition to development of tumors from various germ layers.

Adult↗

PubMed1992

Interaction of Wnt and activin in dorsal mesoderm induction in Xenopus.

Both the activin and Wnt families of peptide growth factors are capable of inducing dorsal mesoderm in Xenopus embryos. Presumptive ventral ectoderm cells isolated from embryos injected with Xwnt8 mRNA were cultured in the presence of activin A to study the possible interactions between these two classes of signaling proteins. We find that overexpression of Xwnt8 RNA alters the response of ventral ectoderm to activin such that ventral explants differentiate dorsoanterior structures including notochord and eyes. This response is similar to the response of dorsal ectoderm to activin alone. When embryos are irradiated with uv light to inhibit dorsal axis formation, ectodermal explants differentiate notochord when they are induced by a combination of both signaling factors, but not when cells receive only one inducing signal (activin or Xwnt8). This result is further supported by the observation that goosecoid (gsc) mRNA, an early marker for dorsal mesoderm, is expressed in these explants only when they are injected with Xwnt8 mRNA followed by exposure to activin. Early morphogenetic movements of the induced cells and activation of muscle-specific actin and Brachyury (Xbra) genes also reveal a cooperation of activin A and Xwnt8 in mesoderm induction.

Actins↗

PubMed1987

The relation between mixed mesodermal tumors and adenocarcinomas of the ovary. An immunopathologic study.

Mixed mesodermal tumor of the ovary is a rare neoplasm. The diagnosis is made if an ovarian carcinoma contains heterologous sarcomatous differentiation. With the help of an immunopathologic stain for desmin, the intermediate filament protein of muscle cells, twenty cases of ovarian adenocarcinoma were examined for the presence of morphologically unrecognizable heterologous tumor cells. Six of twenty tumors were positive. There was no significant correlation between a number of clinical parameters and desmin positivity. The authors conclude that mixed mesodermal tumor of the ovary may not be a separate entity. Instead, there may be a single group of ovarian epithelial tumors ranging from borderline or well-differentiated carcinomas to poorly-differentiated tumors which may show homologous (carcinosarcoma) or heterologous (mixed mesodermal tumor) differentiation.

Adenocarcinoma↗

PubMed1990

The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans.

Three known genes guide circumferential migrations of pioneer axons and mesodermal cells on the nematode body wall. unc-5 affects dorsal migrations, unc-40 primarily affects ventral migrations, and unc-6 affects migrations in both directions. Circumferential movements still occur, but are misdirected whereas longitudinal movements are normal in these mutants. Pioneer growth cones migrating directly on the epidermis are affected; growth cones migrating along established axon fascicles are normal. Thus these genes affect cell guidance and not cell motility per se. We propose that two opposite, adhesive gradients guide circumferential migrations on the epidermis. unc-5, unc-6, and unc-40 may encode these adhesion molecules or their cellular receptors. Neurons have access to the basal lamina and the basolateral surfaces of the epidermis, but mesodermal cells contact only the basal lamina. These genes probably identify molecular cues on the basal lamina that guide mesodermal migrations. The same basal lamina cues, or perhaps related molecules on the epidermal cell surfaces, guide pioneer neurons.

Animals↗

PubMed2003

Eph/Ephrin signaling regulates the mesenchymal-to-epithelial transition of the paraxial mesoderm during somite morphogenesis.

BACKGROUND: During somitogenesis, segmental patterns of gene activity provide the instructions by which mesenchymal cells epithelialize and form somites. Various members of the Eph family of transmembrane receptor tyrosine kinases and their Ephrin ligands are expressed in a segmental pattern in the rostral presomitic mesoderm. This pattern establishes a receptor/ligand interface at each site of somite furrow formation. In the fused somites (fss/tbx24) mutant, lack of intersomitic boundaries and epithelial somites is accompanied by a lack of Eph receptor/Ephrin signaling interfaces. These observations suggest a role for Eph/Ephrin signaling in the regulation of somite epithelialization. RESULTS: We show that restoration of Eph/Ephrin signaling in the paraxial mesoderm of fss mutants rescues most aspects of somite morphogenesis. First, restoration of bidirectional or unidirectional EphA4/Ephrin signaling results in the formation and maintenance of morphologically distinct boundaries. Second, activation of EphA4 leads to the cell-autonomous acquisition of a columnar morphology and apical redistribution of beta-catenin, aspects of epithelialization characteristic of cells at somite boundaries. Third, activation of EphA4 leads to nonautonomous acquisition of columnar morphology and polarized relocalization of the centrosome and nucleus in cells on the opposite side of the forming boundary. These nonautonomous aspects of epithelialization may involve interplay of EphA4 with other intercellular signaling molecules. CONCLUSIONS: Our results demonstrate that Eph/Ephrin signaling is an important component of the molecular mechanisms driving somite morphogenesis. We propose a new role for Eph receptors and Ephrins as intercellular signaling molecules that establish cell polarity during mesenchymal-to-epithelial transition of the paraxial mesoderm.

Animals↗

PubMed1985

Malignant mixed mesodermal tumor of bladder occurring after radiotherapy for cervical cancer: report of a case.

A rare case of radiation-induced malignant mixed mesodermal tumor of the bladder is reported. A 78-year-old woman complained of hematuria, which originated from a polypoid tumor in the bladder 15 years after radiotherapy for squamous cell carcinoma of the uterine cervix. The bladder tumor recurred 9 months after resection and partial cystectomy then was performed. Histological findings revealed malignant mixed mesodermal tumor composed of carcinomatous and sarcomatous elements. The former element consisted mainly of transitional cell carcinoma with occasional foci of squamous metaplasia and glandular differentiation, while the latter consisted of spindle cell sarcoma showing partly cartilaginous and osseous differentiation. The histogenesis of malignant mixed mesodermal tumor of the bladder also is discussed.

Aged↗

PubMed1999

Evidence that FGF receptor signaling is necessary for endoderm-regulated development of precardiac mesoderm.

Endoderm cells in the heart forming region (HFR endoderm) of stage 6 chicken embryos are required to support the proliferation and terminal differentiation of precardiac mesoderm cells in vitro. The endoderm's effect can be substituted by growth factors, including members of the fibroblast growth factor (FGF) family. However, direct implication of FGFs in this process requires evidence that inhibition of FGF signaling interferes with proliferation and/or terminal differentiation. This report examines the consequences of treating endoderm/precardiac mesoderm co-explants with agents that inactivate FGF receptors. Using sodium chlorate, which prevents FGF ligand-receptor interaction, it was observed that the percentage of S-phase precardiac mesoderm cells was markedly reduced, suggesting that cell proliferation was inhibited. To more specifically affect FGF signaling, the explants were treated with an antibody that recognizes an extracellular domain of FGF receptor-1 (FGFR-1). This treatment similarly inhibited cell proliferation. Although both agents modestly delayed cardiac myocyte differentiation as indicated by the contractile function, expression of alpha-sarcomeric actin was not affected. These findings provide additional evidence that an intact FGF signaling pathway is required during heart development.

Animals↗

PubMed1989

Clinicopathologic features of ovarian mixed mesodermal tumors and carcinosarcomas.

Over a 27-year period there were 15 patients treated at the University of Michigan Medical center for carcinosarcomas or mixed mesodermal tumors of the ovary. Overall median survival was 11 months. Median survival was 4 months in patients with carcinosarcomas and 13 months in patients with mixed mesodermal tumors (P = 0.066). Patients with a chondrosarcomatous element had a significantly longer median survival than patients with mixed mesodermal tumors lacking cartilaginous differentiation (P = 0.031). The presence of a rhabdomyosarcomatous element did not affect survival. The size of the primary tumor, presence of ascites, FIGO stage, and degree of initial resection (optimal versus suboptimal) did not affect survival. There was no difference in survival between patients receiving postoperative chemotherapy and patients undergoing postoperative irradiation.

Adult↗

PubMed1999

Spatial expression of Drosophila glutathione S-transferase-D1 in the alimentary canal is regulated by the overlying visceral mesoderm.

Regional gene expression within Drosophila gut epithelium is regulated by the homeotic genes expressed in the overlying visceral mesoderm. Here it is reported that Glutathione S-transferase-D1 (Gst-D1) had three distinctive expression domains in the gut epithelia: the inner epithelium of the proventriculus, the anterior border of the hindgut epithelium, and the midgut epithelium. Gst-D1 expression in the midgut epithelium became restricted to the region that later formed the third midgut constriction. This spatial restriction within the midgut epithelium required abdominal-A activity in the overlying visceral mesoderm, suggesting that Gst-D1 will be a useful marker to analyze the mechanism of gene regulation across the mesoderm and endoderm.

Animals↗

PubMed1992

Benign mesodermal tumors producing nasal deformity.

Tumors of neurogenic (ectodermal) origin are well-described causes of nasal deformity. We present a patient with a benign mesodermal tumor (unclassified spindle cell) producing nasal deformity. A retrospective review of the two senior authors' records provided an additional three patients with nonvascular benign mesodermal nasal masses (fibroma and leiomyoma). Benign mesodermal masses can occur in the midline of the nose and need to be differentiated from dermoids and gliomas. Misdiagnosis is the rule. Excisional biopsy is required for definitive diagnosis. In addition, excisional biopsy is curative and can help to minimize the subsequent nasal deformity if performed early in the disease process. Immunohistochemical and electron microscopy may be required for comprehensive diagnosis and treatment.

Adult↗

PubMed1992

Leiomyosarcomas have a poorer prognosis than mixed mesodermal tumours when adjusting for known prognostic factors: the result of a retrospective study of 423 cases of uterine sarcoma.

OBJECTIVE: To determine the survival data for the various tumour types of uterine sarcoma and determine the influence of various prognostic factors on survival. DESIGN: Retrospective analysis of all uterine sarcoma cases registered in the 15 year period 1967-1981. SETTING: West Midlands Regional Cancer Registry, serving a catchment area of 2.6 million women. SUBJECTS: 423 women registered as having a uterine sarcoma; 367 of these were associated with the two main histological types, leiomyosarcomas (LMS) and mixed mesodermal tumours (MMT). MAIN OUTCOME MEASURES: Duration of survival was taken as the primary endpoint. RESULTS: The overall 5-year survival for uterine sarcomas in this series was 31%, with the major prognostic indicator being tumour stage. Survival for mixed mesodermal tumours is similar to other sarcomas despite a tendency towards less differentiation, wider dissemination and a greater age of the patient at diagnosis. Multivariate analysis shows that for cases with similar stage, age and grade, mixed mesodermal tumours have a better prognosis than leiomyosarcomas. CONCLUSIONS: These results demonstrate the danger of considering each variable in isolation when the relation between variables can lead to spurious significance or lack of significance because of the imbalances in the numbers between groups of prognostic importance. This study underlines the need for an adequate inspection of the intra-abdominal contents at the time of hysterectomy for uterine fibroids.

Adult↗

PubMed2001

Direct regulation of the muscle-identity gene apterous by a Hox protein in the somatic mesoderm.

Hox genes control segment identity in the mesoderm as well as in other tissues. Most evidence indicates that Hox genes act cell-autonomously in muscle development, although this remains a controversial issue. We show that apterous expression in the somatic mesoderm is under direct Hox control. We have identified a small enhancer element of apterous (apME680) that regulates reporter gene expression in the LT1-4 muscle progenitors. We show that the product of the Hox gene Antennapedia is present in the somatic mesoderm of the second and third thoracic segments. Through complementary alterations in the Antennapedia protein and in its binding sites on apME680, we show that Antennapedia positively regulates apterous in a direct manner, demonstrating unambiguously its cell-autonomous role in muscle development. Finally, we determine that LT1-4 muscles contain more nuclei in the thorax than in the abdomen and we propose that one of the segmental differences under Hox control is the number of myoblasts allocated to the formation of specific muscles in different segments.

Animals↗