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Biomedical subjects

I Godin

Publications and source records attributed to I Godin.

30 records · Page 2Linked to original sources

[Intra-embryonic hematopoiesis in mice].

In vertebrate embryos, all hemopoietic tissues that are successively active during ontogeny (fetal liver, thymus, spleen and bone marrow) are colonized by extrinsic hemopoietic stem cells (HSC). The exception to this rule is the yolk sac (YS) whose progenitors arise in situ. Moreover, the YS is the first hemopoietic site to appear in the embryo. In consequence, it was considered as the primary source of the HSC that transfer from one site to the other until the demonstration that, in birds, the source of definitive HSC was located in the aortic region of the embryo. To assess a possible contribution of intraembryonic sites to mouse hemopoietic development, we developed an in vitro approach that permits the detection of multipotent hemopoietic progenitors in the region surrounding the dorsal aorta. This new site, the paraaortic splanchnopleura (P-Sp), is active from the 10 somite stage to the stage of fetal liver colonization by HSC. The in vitro analysis of the hemopoietic potential of the P-Sp revealed that: 1) progenitors present in this region are multipotent since a single micromanipulated P-Sp cell can give rise to mature B and T lymphocytes and various myeloid cells, when cultivated in appropriate conditions; 2) the P-Sp is the only intraembryonic site endowed with this potential; 3) numbering progenitors present in the YS and P-Sp indicated that precursors appear in both locations at the 10-12 somite stage reaching 15 in each site at 9.5 dpc (25 somites), shortly before the beginning of fetal liver colonisation. During a cytological study of the 9-11 dpc embryo aimed to disclose the cellular basis for our experimental results, two potential hemopoietic sites were uncovered. Cells clusters that resemble avian intraaortic hemopoietic clusters were found in the arteries located close to the coelomic cavity (dorsal aorta, umbilical and omphalomesenteric arteries). Moreover, groups of cells strikingly similar to YS blood islands were uncovered in the mesentery. All these sites are located in areas formed from the P-Sp and are fully developed at the onset of fetal liver colonization. These hemogenic sites most probably develop from the hemopoietic precursors present in the P-Sp.

Animals↗

Developmental relationships between hemopoiesis and vasculogenesis.

Using avian chimeras, we have demonstrated earlier that the stem cells seeding the definitive hemopoietic organs form within the embryo rather than in the yolk sac. We now report experimental evidence indicating that hemopoietic progenitors appear in mouse embryos in the para-aortic splanchnopleura, a location similar to the one that produces stem cells in avian embryos. This structure obtained from E8.5 embryos was grafted under the kidney capsule of adult SCID mice. One compartment of the B lymphoid system became reconstituted with cells derived from the graft, that were identified with genetic and antigenic markers. In vitro data are also in favor of the production of progenitors from this structure. Finally a strategy designed to understand the developmental links between the endothelial network and hemopoietic cells is described. It is based on the expression patterns of two protooncogenes, c-ets1 and c-myb, activated during the amplification period of each of these lineages.

Animals↗

Effects of the steel gene product on mouse primordial germ cells in culture.

Mutations at the steel (sl) and dominant white spotting (W) loci in the mouse affect primordial germ cells (PGC), melanoblasts and haemopoietic stem cells. The W gene encodes a cell-surface receptor of the tyrosine kinase family, the proto-oncogene c-kit. In situ analysis has shown c-kit messenger RNA expression in PGC in the early genital ridges. The Sl gene encodes the ligand for this receptor, a peptide growth factor, called here stem cell factor (SCF). SCF mRNA is expressed in many regions of the early mouse embryo, including the areas of migration of these cell types. It is important now to identify the role of the Sl-W interaction in the development of these migratory embryonic stem cell populations. Using an in vitro assay system, we show that SCF increases both the overall numbers and colony sizes of migratory PGC isolated from wild-type mouse embryos, and cultured on irradiated feeder layers of STO cells (a mouse embryonic fibroblast line). In the absence of feeder cells, SCF causes a large increase in the initial survival and apparent motility of PGC in culture. But labelling with bromodeoxyuridine shows that SCF is not, by itself, a mitogen for PGC. SCF does not exert a chemotropic effect on PGC in in vitro assays. These results suggest that SCF in vivo is an essential requirement for PGC survival. This demonstrates the control of the early germ-line population by a specific trophic factor.

Animals↗

TGF beta 1 inhibits proliferation and has a chemotropic effect on mouse primordial germ cells in culture.

Primordial germ cells are the stem cells that provide the functional gametes of adult animals. In many animal groups they are set aside at the earliest stages of development, and migrate from their sites of first appearance to the sites where the gonad will form, the genital ridges. During this migration they proliferate. In the mouse embryo their numbers increase from less than one hundred to approximately four thousand during the period of their migration. In a previous paper we showed that both the proliferation and the direction of migration of mouse PGCs in culture were influenced by soluble factors released from their target tissue, the genital ridges. Studies on other stem cell populations have shown that complex combinations of growth factors control their proliferation, migration and differentiation. In this paper, we show that TGF beta 1 inhibits proliferation of PGCs taken from 8.5 day old embryos and cultured on embryonic fibroblast feeder layers. We also show that the previously reported chemotropic effect of genital ridges in this culture system is mediated by TGF beta 1, or a closely related molecule, released from the genital ridges.

Animals↗

Health and social inequities in Belgium.

This paper presents two different yet complementary on-going studies related to the understanding of the mechanisms leading to social inequalities in health. The first part is devoted to a differential morbidity survey held in southern Belgium. It confirms that striking differences exist in the period around birth between social categories, and between the three districts under study. In a multivariate approach, differences remain between the social categories and between the district samples, which classically studied socio-demographical, behavioural and medical characteristics cannot fully explain. The role of cultural factors is analysed and discussed through the concept of 'health culture' and alternative hypotheses are reviewed in the light of the results. The second part reviews the studies conducted on the so-called avoidable mortality in the EEC and more specifically in Belgium. The concept of avoidable mortality is discussed, as well as its utility from the standpoint of the present concern on social inequalities. Differences between EEC countries are large, and even within Belgium there are important disparities between the districts. The role of health care supply has not been demonstrated yet in these two contexts. For Belgium, it appears that a major part of the unequally distributed mortality is constituted by causes of death considered as avoidable. Moreover, the most discriminating causes of death are overrepresented in socially deprived districts. The two perspectives are confronted in order to delineate perspectives for future research and operational outcomes for policy making and interventions.

Belgium↗

Genital ridges exert long-range effects on mouse primordial germ cell numbers and direction of migration in culture.

The functional gametes of all vertebrates first arise in the early embryo as a migratory population of cells, the primordial germ cells (PGCs). These migrate to, and colonise, the genital ridges (GR) during the early organogenesis period, giving rise to the complete differentiating gonad. PGCs first become visible by alkaline phosphatase staining in the root of the developing allantois at 8.5 days post coitum (dpc). At 9.5 dpc they are found in the wall of the hind-gut and, during the following three days, they migrate along the hind-gut mesentery to the dorsal body wall, and then to the genital ridges. By 12.5 dpc, the great majority of PGCs have colonised the genital ridges. During this period the number of PGCs increases from less than 100 to approximately 4000. In a previous paper (Donovan et al. 1986), we showed that 10.5 dpc PGCs can be explanted from the hind-gut mesentery, and will spread and migrate on feeder cell layers. We showed also that the intrinsic ability of PGCs to spread and migrate changes as they colonise the genital ridges. In this paper, we examine extrinsic factors that control PGC behaviour in vitro. Using PGCs taken from 8.5 dpc embryos, at the beginning of their migratory phase, we show that culture medium conditioned by 10.5 dpc genital ridges causes an increase in the number of PGCs in these cultures. We also show that PGCs migrate towards 10.5 dpc genital ridges in preference to other explanted organs. These experiments show that genital ridges exert long-range effects on the migrating population of PGCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Maternal and child health in the Fourth World. Initial results of a socio-epidemiological survey].

This paper presents the results of a qualitative survey of young mothers in deprived conditions, which was conducted as a part of a broader socio-epidemiological research on health inequalities amongst mother and child. This survey reveals that this group is not solely distinguished in terms of socio-economic categories. Cultural dimensions play also an important role in explaining their health related behaviour. The survey was aimed at determining the logic and principles of coping with health and sickness. The specific attitudes and behaviour of the survey group was described through fourteen dimensions (definition and perception of health, prevention, relations with professionals, networks used...). The results show that any approach of the health problems of this group has to take its specific health culture into account and that this approach is inevitable in any effort to promote health and reduce social inequalities for the so-called "Fourth World".

Adult↗

Studies on the migration of mouse germ cells.

Primordial germ cells in the mouse embryo migrate from their site of origin to the gonad where they differentiate, giving rise eventually to the gametes of the mature adult animal. The migratory phase is transient and therefore permits analysis of factors regulating the motile activity of cells in tissues. Germ cells can be isolated during migration and cultured on feeder cells of an established cell line (STO). In this system the molecular interactions mediating germ cell adhesion can be probed using antibodies to both germ cell surface determinants and to extracellular matrix components.

Animals↗

Explanted and implanted notochord of amphibian anuran embryos. Histofluorescence study on the ability to synthesize catecholamines.

The notochord of amphibian anuran embryos contains catecholamines during the early developmental stages. In order to determine if these catecholamines are synthesized in situ, the development of their specific histofluorescence was investigated in the notochord alone or the notochord combined with the lateral somitic mesoderm, both explanted at the neurula stage and cultivated in vitro or implanted into the ventral part of early neurulae endoderm. The histofluorescence evolution, on the other hand, was investigated in the notochord alone or combined with myotomes, both explanted after the beginning of catecholamine biosynthesis and cultivated in vitro for one hour, in order to determine the effect of explantation and culture on the accumulation of notochordal catecholamines. The comparative study of catecholamine histofluorescence in these different samples shows that: the notochord is able to perform, on its own, the entire biosynthesis of the catecholamines stored in it during the early developmental stages. The catecholamines generated from isolated notochords tend to diffuse into the culture medium, probably due to a deficiency in the vesicular storage system usually found in the catecholamine-synthesizing cells. This loss of catecholamines in vitro can be obviated by the presence round the notochord of any embryonal tissue (somitic mesoderm, endoderm).

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