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At least 217 records · Page 12Linked to original sources
PubMed2005

Perfusion cultures of human embryonic stem cells.

Human embryonic stem cells (hESC) are self-renewing pluripotent cells capable of differentiating into cells representative of all three embryonic germ layers. Hence, they hold great potential for regenerative medicine. However, significant cell numbers are required to fulfill their potential therapeutic applications. In this study, perfusion with supplemented conditioned media (SCM), produced by mouse embryonic fibroblasts (MEF), was adopted to improve cell densities of hESC cultures. Perfusion enhanced hESC numbers by 70% compared to static conditions, on both organ culture dish (OCD) and petri dish cultures. All cultures maintained healthy expression of the pluripotent marker, Oct-4 transcription factor. In vivo, perfused hESC formed teratomas in severe combined immunodeficiency (SCID) mice models that represent the three embryonic germ layers. When SCM was produced with lower concentrations of MEF, hESC densities and Oct-4 levels were reduced. Hence, perfusion with SCM is a potential feeding method for scale-up production of hESC.

Animals↗
PubMed2006

Canonical Wnt signaling is required for development of embryonic stem cell-derived mesoderm.

Formation of mesoderm from the pluripotent epiblast depends upon canonical Wnt/beta-catenin signaling, although a precise molecular basis for this requirement has not been established. To develop a robust model of this developmental transition, we examined the role of Wnt signaling during the analogous stage of embryonic stem cell differentiation. We show that the kinetics of Wnt ligand expression and pathway activity in vitro mirror those found in vivo. Furthermore, inhibition of this endogenous Wnt signaling abrogates the functional competence of differentiating ES cells, reflected by their failure to generate Flk1(+) mesodermal precursors and subsequent mature mesodermal lineages. Microarray analysis at various times during early differentiation reveal that mesoderm- and endoderm-associated genes fail to be induced in the absence of Wnt signaling, indicating a lack of germ layer induction that normally occurs during gastrulation in vivo. The earliest genes displaying Wnt-dependent expression, however, were those expressed in vivo in the primitive streak. Using an inducible form of stabilized beta-catenin, we find that Wnt activity, although required, does not autonomously promote primitive streak-associated gene expression in vitro. Our results suggest that Wnt signaling functions in this model system to regulate the thresholds or stability of responses to other effector pathways and demonstrate that differentiating ES cells represent a useful model system for defining complex regulatory interactions underlying primary germ layer induction.

Animals↗
PubMed2006

[Clonal culture of rat bone marrow-derived multipotential adult progenitor cells and study of their biological properties].

OBJECTIVE: To optimize the culture conditions for clonal isolation of rat bone marrow-derived multipotential adult progenitor cells (rMAPC) and identify their surface markers and differentiation potentials. METHODS: By using a low concentration of fetal bovine serum culture medium, rMAPCs were primarily isolated from bone marrow by attachment culture and clonal-like cells were selected by single cell limiting dilution. The surface antigens of the cloned rMAPC were analyzed by flow cytometry and immunocytochemistry. Multi-differentiation capacities were evaluated by lipoblasts and osteoblasts and neuroblasts differentiation induction. The expressions of Oct-4 and three embryonic germ layer markers were detected by RT-PCR. RESULTS: Single cell-derived rMAPC could be expanded to passage 20 in vitro which still maintained active proliferation ability. The expanded rMAPCs expressed CD71, alpha-SMA and vimentin, but not CD34, CD44 and CD45. About 83% of the rMAPCs was in the resting phase(G0 + G1) of cell cycle and 17% in S + G2 + M phase. They could be induced to differentiate into adipogenic cells, osteogenic cells and neural like cells. RT-PCR demonstrated that there were expressions of oct-4 gene and three embryonic germ layer markers on the rMAPCs. CONCLUSIONS: Cloned rMAPC can maintain the phenotypes of stem cell during in vitro culturing. It might be an potential adult stem cell source for therapeutic stem cell transplanting and tissue engineering.

Animals↗
PubMed1992

Isolation of Sna, a mouse gene homologous to the Drosophila genes snail and escargot: its expression pattern suggests multiple roles during postimplantation development.

The Drosophila gene snail encodes a zinc-finger protein that is required zygotically for mesoderm formation. Snail acts as a transcriptional repressor during the period of mesoderm formation by preventing expression of mesectodermal and ectodermal genes in the mesoderm anlage. A Xenopus homolog (xsnail) of snail has been cloned and it too is expressed early in the mesodermal germ layer. We have isolated cDNA clones of a mouse gene (termed Sna) closely related to snail and xsnail and another Drosophila gene termed escargot that also encodes a zinc-finger protein. Sna encodes a 264 amino acid protein that contains four zinc fingers. Developmental RNA blot analysis showed that Sna transcripts are expressed throughout postimplantation development. Analysis of the spatial and temporal localization of Sna transcripts by in situ hybridization to both whole-mount and sectioned embryos revealed that, in the gastrulating embryo, Sna is expressed throughout the primitive streak and in the entire mesodermal germ layer. By 9.5 days post coitum (dpc) Sna is expressed at high levels in cephalic neural crest and limb bud mesenchyme. In fact, by 10.5 dpc Sna expression is observed in most mesenchymal cells, whether of neural crest or mesodermal origin. Later in gestation, high levels of Sna expression are observed in condensing cartilage and in the mesenchymal component of several tissues (lung, kidney, teeth and vibrissae) that undergo epithelial-mesenchymal inductive interactions during development. These results suggest multiple roles for the Sna gene in gastrulation and organogenesis during murine development.

Amino Acid Sequence↗
PubMed1997

Fates of the blastomeres of the 32-cell stage Pleurodeles waltl embryo.

Cell fate of the blastomeres at the 32-cell stage in the Pleurodeles waltl embryo was analyzed by injection of rhodamine or fluorescein lysinated-dextran (RLDx or FLDx). At the tailbud stage, the progeny of each blastomere contributed to more than one germ layer with unequal distribution along the anteroposterior and dorsoventral axis. Such a regionalized positioning of the descendants of the 32-cell blastomeres was found in the neuroectoderm, the epidermis, the notochord, the somites, the lateral plate, and the endoderm, but not in the head mesenchyme, the pronephros, or the blood islands. Results of double labeling of juxtaposed blastomeres showed that cell mixing and rearrangement take place during organ formation. Results are compared with those of the 32-cell stage fate map in Xenopus and Rana and reveal the more restricted fate of 32-cell stage blastomeres in Pleurodeles germ layers.

Animals↗
PubMed1995

Induction of prostatic morphology and secretion in urothelium by seminal vesicle mesenchyme.

Mesenchymal-epithelial interactions are essential for the development of the male reproductive tract. Tissue recombination experiments have been used to define the characteristics of these interactions. When mesenchyme, embryonic connective tissue, is recombined with epithelium from another organ an instructive induction may occur in which the developmental fate of the epithelium is altered. Instructive inductions are most common when the epithelium that is removed from the mesenchyme and the epithelium that is recombined with the mesenchyme are from the same germ layer. All of the mesenchyme of the male reproductive tract is of mesodermal origin. The epithelia of these organs are derived from either the mesodermal Wolffian duct epithelium or the endodermal urogenital sinus epithelium. Urogenital sinus mesenchyme can instructively induce bladder and urethral epithelium to form prostate (Donjacour, A. A. and Cunha, G. R. (1993) Endocrinol. 132, 2342-2350) and seminal vesicle mesenchyme can instructively induce epithelium from the ductus deferens and ureter (Cunha, G. R., Young, P., Higgins, S. J. and Cooke, P. S. (1991) Development 111, 145-158) to form seminal vesicle. To see whether inductive interactions could occur across germ layers in this system, seminal vesicle mesenchyme, normally associated with a mesodermal epithelium, was recombined with epithelium from neonatal or adult bladder or urethra, which are of endodermal origin. The resulting tissue recombinants were analyzed histologically and by immunocytochemistry and western blotting with antibodies to prostatic and seminal vesicle secretory proteins. Full prostatic differentiation was observed in tissue recombinants made with seminal vesicle mesenchyme plus either adult or neonatal bladder or urethral epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen-Insensitivity Syndrome↗
PubMed2006

Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest.

Metazoans are composed of a finite number of recognisable cell types. Similar to the relationship between species and ecosystems, knowledge of cell type diversity contributes to studies of complexity and evolution. However, as with other units of evolution, the cell type often resists definition. This review proposes guidelines for characterising cell types and discusses cell homology and the various developmental pathways by which cell types arise, including germ layers, blastemata (secondary development/neurulation), stem cells, and transdifferentiation. An updated list of cell types is presented for a familiar, albeit overlooked model taxon, adult Homo sapiens, with 411 cell types, including 145 types of neurons, recognised. Two methods for organising these cell types are explored. One is the artificial classification technique, clustering cells using commonly accepted criteria of similarity. The second approach, an empirical method modeled after cladistics, resolves the classification in terms of shared features rather than overall similarity. While the results of each scheme differ, both methods address important questions. The artificial classification provides compelling (and independent) support for the neural crest as the fourth germ layer, while the cladistic approach permits the evaluation of cell type evolution. Using the cladistic approach we observe a correlation between the developmental and evolutionary origin of a cell, suggesting that this method is useful for predicting which cell types share common (multipotential) progenitors. Whereas the current effort is restricted by the availability of phenotypic details for most cell types, the present study demonstrates that a comprehensive cladistic classification is practical, attainable, and warranted. The use of cell types and cell type comparative classification schemes has the potential to offer new and alternative models for therapeutic evaluation.

Evolution, Molecular↗
PubMed2000

Eomesodermin is required for mouse trophoblast development and mesoderm formation.

The earliest cell fate decision in the mammalian embryo separates the extra-embryonic trophoblast lineage, which forms the fetal portion of the placenta, from the embryonic cell lineages. The body plan of the embryo proper is established only later at gastrulation, when the pluripotent epiblast gives rise to the germ layers ectoderm, mesoderm and endoderm. Here we show that the T-box gene Eomesodermin performs essential functions in both trophoblast development and gastrulation. Mouse embryos lacking Eomesodermin arrest at the blastocyst stage. Mutant trophoectoderm does not differentiate into trophoblast, indicating that Eomesodermin may be required for the development of trophoblast stem cells. In the embryo proper, Eomesodermin is essential for mesoderm formation. Although the specification of the anterior-posterior axis and the initial response to mesoderm-inducing signals is intact in mutant epiblasts, the prospective mesodermal cells are not recruited into the primitive streak. Our results indicate that Eomesodermin defines a conserved molecular pathway controlling the morphogenetic movements of germ layer formation and has acquired a new function in mammals in the differentiation of trophoblast.

Amino Acid Sequence↗
PubMed2000

Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture.

Embryonic stem (ES) cell lines derived from human blastocysts have the developmental potential to form derivatives of all three embryonic germ layers even after prolonged culture. Here we describe the clonal derivation of two human ES cell lines, H9.1 and H9.2. At the time of the clonal derivation of the H9.1 and H9.2 ES cell lines, the parental ES cell line, H9, had already been continuously cultured for 6 months. After an additional 8 months of culture, H9.1 and H9.2 ES cell lines continued to: (1) actively proliferate, (2) express high levels of telomerase, and (3) retain normal karyotypes. Telomere lengths, while somewhat variable, were maintained between 8 and 12 kb in high-passage H9.1 and H9.2 cells. High-passage H9.1 and H9.2 cells both formed teratomas in SCID-beige mice that included differentiated derivatives of all three embryonic germ layers. These results demonstrate the pluripotency of single human ES cells, the maintenance of pluripotency during an extended period of culture, and the long-term self-renewing properties of cultured human ES cells. The remarkable developmental potential, proliferative capacity, and karyotypic stability of human ES cells distinguish them from adult cells.

Adult↗
PubMed2004

Derivation, propagation and differentiation of human embryonic stem cells.

Embryonic stem (ES) cells are in vitro cultivated pluripotent cells derived from the inner cell mass (ICM) of the embryonic blastocyst. Attesting to their pluripotency, ES cells can be differentiated into representative derivatives of all three embryonic germ layers (endoderm, ectoderm and mesoderm) both in vitro and in vivo. Although mouse ES cells have been studied for many years, human ES cells have only more recently been derived and successfully propagated. Many biochemical differences and culture requirements between mouse and human ES cells have been described, yet despite these differences the study of murine ES cells has provided important insights into methodologies aimed at generating a greater and more in depth understanding of human ES cell biology. One common feature of both mouse and human ES cells is their capacity to undergo controlled differentiation into spheroid structures termed embryoid bodies (EBs). EBs recapitulate several aspects of early development, displaying regional-specific differentiation programs into derivatives of all three embryonic germ layers. For this reason, EB formation has been utilised as an initial step in a wide range of studies aimed at differentiating both mouse and human ES cells into a specific and desired cell type. Recent reports utilising specific growth factor combinations and cell-cell induction systems have provided alternative strategies for the directed differentiation of cells into a desired lineage. According to each one of these strategies, however, a relatively high cell lineage heterogeneity remains, necessitating subsequent purification steps including mechanical dissection, selective media or fluorescent or magnetic activated cell sorting (FACS and MACS, respectively). In the future, the ability to specifically direct differentiation of human ES cells at 100% efficiency into a desired lineage will allow us to fully explore the potential of these cells in the analysis of early human development, drug discovery, drug testing and repair of damaged or diseased tissues via transplantation.

Animals↗
PubMed2004

Expression of estrogen receptor-alpha and -beta, glucocorticoid receptor, and progesterone receptor genes in human embryonic stem cells and embryoid bodies.

Human embryonic stem cells (hESCs) have the potential to differentiate into various cell types, and the three germ layers in vivo and in vitro. They are therefore useful in transplantation and tissue engineering. Here, we describe the expression patterns of selected steroid receptor mRNAs - estrogen receptor-alpha (ER-alpha), ER-beta, glucocorticoid receptor (GR), and progesterone receptor (PR) - in undifferentiated hESCs and embryoid bodies (EBs) cultured for 2, 4, and 6 d, as assessed by real-time PCR, in order to define the possible influence of steroid hormones on the differentiation of hESCs. These receptor mRNAs were expressed in undifferentiated hESCs and EBs. The expression of PR mRNA only decreased during the differentiation of EBs but not of hESCs. Immunohistochemical analysis gave strong staining of ER-alpha, ER-beta, and GR proteins in the nuclei of hESCs and EBs, whereas PR was not detected. We also examined the potential of these steroid hormones to direct the differentiation of hESCs in vitro. The expression of 11 cell-specific markers representing 3 germ layers and 5 tissue types was used to assess the differentiation of hESCs. We found that certain endodermal marker genes were either only expressed in the estrogen-treated group or their expression was stimulated in that group, suggesting that steroid hormones can control the differentiation of hESCs into various cell types.

Animals↗
PubMed2002

The origin of mesoderm in phoronids.

Descriptive studies of phoronid development have concluded that the mesoderm of these animals originates from the endoderm during gastrulation. This interpretation has been tested by labeling one blastomere of 4- through 16-cell embryos and examining the position and germ layers occupied by the labeled clones of cells in the larva. No 2 injections gave rise to identical clones of cells, suggesting that the cleavage program does not generate cells of unique identity and that cell fates are established at later developmental time points. In many cases, a relatively large sector composed of ectodermal cells was labeled. When these labeled cells were adjacent to the mouth or anus of the larva, muscle and mesenchyme cells originated from the labeled clones. Under these circumstances, nerve cells also originated from these labeled sectors. These labeling studies also showed that endodermal cells can give rise to mesodermal and neural cells. These results suggest that nerve and muscle cells are induced to form at ectodermal-endodermal boundaries from both germ layers. These marking experiments also confirmed the observation that nerve cells originate both from the apical organ and the trunk region and show for the first time that the intestine originates by ingression of posterior ectoderm.

Animals↗
PubMed1998

Differential expression of sea urchin Otx isoform (hpOtxE and HpOtxL) mRNAs during early development.

Two distinct types of orthodenticle-related proteins (early type: HpOtxE, late type: HpOtxL) of the sea urchin, Hemicentrotus pulcherrimus, have been implicated as enhancer element binding factors of the aboral ectoderm-specific arylsulfatase (HpArs) gene. In order to understand the role of these isoforms during sea urchin development, we have isolated and characterized HpOtx gene. Here we describe the spatial expression patterns of HpOtxE and HpOtxL mRNAs and effects of overexpression of these mRNAs on embryogenesis. Whole-mount in situ hybridization using each isoform-specific probe reveals the complex and dynamic change of expression patterns among three germ layers. HpOtxE mRNA is maternally stored and exists apparently in a nonlocalized manner by the blastula stage. After hatching, HpOtxE transcripts are expressed predominantly in presumptive endoderm cells and gradually decrease during gastrulation. Signals for HpOtxL mRNA are intense at the vegetal half after hatching and subsequently, its expression is restricted to the micromere-derived cells. After primary mesenchyme cell (PMC) ingression, HpOtxL transcripts are localized at the vegetal plate and thereafter, concentrated primarily in ectoderm. Eggs injected with HpOtxE or HpOtxL mRNA develop into similar radialized structures without PMC ingression and gut invagination, whose oral-aboral axes are disrupted. Overexpression of HpOtxE induces accumulation of HpOtxL mRNA at the significantly earlier stages, though HpOtxL overexpression inhibits the accumulation of HpOtxE transcripts. Expression patterns of HpOtxE and HpOtxL in all three germ layers and dramatic morphological changes observed in the mRNA-injected embryos suggest that each HpOtx isoform has an important role in sea urchin embryogenesis.

Animals↗
PubMed1975

Pathogenesis of teratoid tumors of the ovary and testis.

Based upon a representative sample of testicular tumors studied at the Armed Forces Institute of Pathology, several testicular and ovarian tumors observed in Denver, pertinent papers in the literature, and the singular thesis of Chevassu on tumors of the testis, the pathogenesis of such neoplasms is elaborated. The findings are philosophical, speculative, and established. Man is a multicellular individual to be regarded as a vehicle for the transmission of unicellular organisms or germ cells from one generation to the next. These cells remain distinct from somatic and trophoblastic cells. The mature human female not only tolerates the normal expression of the fertilized ovum during pregnancy (sex cells, blastoderm, and trophoblast) but also seems capable of greater differentiation of immature somatic cells resulting from parthenogenesis of one or more ova into cells of the three germ layers, as well as the suppression of the growth of neoplastic sex cells and trophoblast cells, with benign cystic teratoma as the most common culmination. The preponderance of malignant teratoid tumors before sexual maturity is a corollary. In contrast, the human male is not equipped with organizers postulated for the human female and thus is unable to differentiate malignant immature somatic cells, the most common cancerous element in testicular tumors. The explanation for such neoplasms must be on the basis of segregation of such cells and abnormal spermatogonia or less often trophoblastic cells in the embryo, with later expression as neoplastic cells, since spermatogonia and progeny are unable to form a new individual. To paraphrase Wilms, the statement may be made that malignant testicular and ovarian tumors of teratoid type are related, despite their different microscopic appearance, to a common form. They differ only in the quality, not in the quantity, of the different tissues comprising them. These tumors contain neoplastic blastodermic cells and differentiated cells of the three germ layers, neoplastic sex cells, and neoplastic trophoblastic cells. The cells of these tumors and the tissues they form resemble very nearly the tissues of the human embryo with nonaxial formation of alimentary and respiratory structures in many instances. The notable frequency of variably differentiated neural elements in the teratoids tumors of the ovary is in sharp contrast to their uncommon occurrence in like tumors of the testis. Dysgenesis of the ovaries and the testes of testicular feminization syndrome should be regarded as likely soil for the development of teratoid tumors.

Adolescent↗
PubMed2006

Tissue specific distribution of the 3243A->G mtDNA mutation.

BACKGROUND: The 3243A-->G is a common pathogenic mitochondrial DNA (mtDNA) point mutation causing a variety of different phenotypes. Segregation of this mutation to different tissues during embryonic life and postnatally is still enigmatic. OBJECTIVE: To investigate the tissue distribution of this mutation. METHODS: In 65 individuals from nine families segregating the 3243A-->G mutation, the mutation load (% mutated mtDNA) was determined in various tissues. Mutation load was measured in two to four cell types--blood leucocytes, buccal cells, skeletal muscle cells, and urine epithelial cells (UEC)--derived from all three embryogenic germ layers. RESULTS: There was a significant correlation among mutation loads in the four tissues (r = 0.80-0.89, p<0.0001). With blood serving as reference, the mutation load was increased by 16% in buccal mucosa, by 31% in UEC, and by 37% in muscle. There were significant differences between the mitotic tissues blood, buccal mucosa, and UEC (p<0.0001), but no difference between UEC and muscle. Using the present data as a cross sectional investigation, a negative correlation of age with the mutation load was found in blood, while the mutation load in muscle did not change with time; 75% of the children presented with higher mutation loads than their mothers in mitotic tissues but not in the post-mitotic muscle. CONCLUSIONS: There appears to be a uniform distribution of mutant mtDNA throughout the three germ layers in embryogenesis. The significant differences between mutation loads of the individual tissue types indicate tissue specific segregation of the 3243A-->G mtDNA later in embryogenesis.

Adolescent↗
PubMed2004

Circulating stem cells and tissue repair.

Stem cells are defined as cells that have clonogenic, self-renewing capacities and the capability to differentiate into multiple cell lineages. Whereas embryonic stem cells are derived from mammalian embryos in the blastocyst stage and can generate terminally differentiated cells of all 3 embryonic germ layers, adult human stem cells are capable of maintaining, generating, and replacing terminally differentiated cells within their own specific tissue as a consequence of physiologic cell turnover or tissue injury. The traditional idea of organ-restricted stem-cell differentiation is now being challenged by the suggestion that adult stem cells retain developmental plasticity. Preclinical and clinical studies described in this review provide evidence that within the blood circulate not only progenitor cells that differentiate into hematopoietic cells, but also stem/progenitor cells which can participate in the homeostasis, repair and replacement of solid organ tissues. In addition to the occurrence of cell fusion, there are 4 suggested mechanisms of adult stem cell differentiation into solid organ cells. Preclinical data support these models particularly that of transdifferentiation as the most likely model, allowing stem/progenitor cells to differentiate across lineage, tissue, and germ layer boundaries. There is increasing evidence that we can manipulate in vivo circulating adult stem cells to repair or regenerate solid organ tissue, which offers potential clinical benefit in the treatment of many hereditary and acquired diseases.

Animals↗
PubMed2002

Neural stem cells: plasticity and their transdifferentiation potential.

The presence of resident stem cells in adult tissues is of fundamental importance for the maintenance of their structural and functional integrity. In fact, throughout life, somatic stem cells attend to the critical function of substituting terminally differentiated cells lost to physiological turnover, injury or disease. Thence, one of the basic dogmata in tissue biology holds that the differentiation potential of an adult stem cell is restricted to the generation of the mature cell lineages found in the tissue to which the stem cell belongs. A plethora of recent evidences from many groups, including ours, is now providing evidence that adult stem cells may possess a broader differentiation repertoire than expected and that their fate potential may not be as tissue specific as once thought. The initial example of an unforeseen, trans-germ layer plasticity - that seems now to emerge as a prototypic functional trait of various somatic stem cells of different origin - has come from the reported awakening of a latent hemopoietic developmental capacity in stem cells isolated from the adult mammalian brain following their transplantation into sub-lethally irradiated mice. More recently, it has been shown that adult neural stem cells can differentiate into a wide array of bodily cells of different origin when injected into the blastocyst and into myogenic cells when transplanted into the adult regenerating skeletal muscle. Moreover, bone marrow stem cells can now give rise to skeletal muscle, hepatic and brain cells, whereas muscle precursors can generate blood cells. In this article, we review some of the basic notions regarding the functional properties of the adult neural stem cells and discuss findings in the expanding area of trans-germ layer conversion, with emphasis on the neural stem cell.

Animals↗
PubMed1989

Relationship between vasculogenesis, angiogenesis and haemopoiesis during avian ontogeny.

Quail-chick intracoelomic grafts of organ rudiments were used to study the origin of endothelia and haemopoietic cells during avian organogenesis in conjunction with the monoclonal antibody QH1 which recognizes the quail haemangioblastic lineage. Results differed according to the germ-layer constitution of the grafted rudiments. In the case of the limb buds, endothelial cells from the host invaded the graft through an angiogenic process. Haemopoietic progenitors from the host also colonized the grafted bone marrow. In contrast, rudiments of internal organs provided their own contingent of endothelial precursors, a process termed vasculogenesis. Nevertheless, haemopoietic cells in these organs were all derived from the host. In the lung, this extrinsic cell population appeared regularly scattered around the parabronchi and had a macrophage-like phenotype. In the pancreas, the granulocytes which differentiate as dense aggregates located in the wall of the largest vessels were extrinsic. Similarly in the spleen, a mesodermal primordium that develops in close association with the pancreatic endoderm, endothelial cells were intrinsic and haemopoietic cells host-derived. This study demonstrates that, in ontogeny, vascularization obeys different rules depending on which germ layer the mesoderm is associated with: in mesodermal/ectodermal rudiments angiogenesis is the rule; in mesodermal/endodermal rudiments, vasculogenesis occurs. However, in these internal organs undergoing vasculogenesis, endothelial and haemopoietic cells have separate origins. We put forward the hypothesis that the endoderm induces the emergence of endothelial cells in the associated mesoderm. Formation of blood stem cells may also involve interactions between endoderm and mesoderm, but in this case the responding capacity of the mesoderm appears restricted to the paraaortic region.

Animals↗