Naive and primed pluripotent states.

Biology of the Mouse Histocompatibility-2 Complex

HEPATOCYTE growth factor/scatter factor (HGF/SF) functions as a mitogen, motogen and morphogen for a variety of cultured cells1–7. The genes for HGF/SF and its receptor (the c-met protooncogene product8) are expressed in many tissues during the embryonic periods and in the adult9–14. HGF/SF is thought to mediate a signal exchange between the mesenchyme and epithelia during mouse development15. To examine the physiological role of HGF/SF, we generated mutant mice with a targeted disruption of the HGF/SF gene. Here we report that homozygous mutant embryos have severely impaired placentas with markedly reduced numbers of labyrinthine trophoblast cells, and die before birth. The growth of trophoblast cells was stimulated by HGF/SF in vitro, and the HGF/SF activity was released by allantois in primary culture of normal but not mutant embryos. These findings suggest that HGF/SF is an essential mediator of allantoic mesenchyme-trophoblastic epithelia interaction required for placental organogenesis.

Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor

https://www.cell.com/cell/pdf/0092-8674(81)90502-X.pdf

The foundation of two distinct cell lineages within the mouse morula

Publisher Summary This chapter discusses the cell polyploidy and its relation to tissue growth and function. Cytophotometry established a fundamental similarity between polyploidy and polyteny, their common feature being multiple doubling of DNA in the cell. The occurrence and properties of polyploid cell populations is discussed. Polyploid nuclei have been found in protozoa and in the cells of many metazoa, both animals and plants. The common property of polyploid cell populations is retention of ability to reproduce DNA by differentiating and often fully differentiated cells. The stem cell phenomenon, which is clearly defined in many diploid cell populations, is in polyploid ones deprived of its main function being the only source of proliferation. The mode of polyploidy is briefly explained. Different types of mitotic polyploidization proper, complete abolition of the mitotic mechanism, and other cases of increases in the DNA content of cells are considered. The mechanism of supplanting mitotic syntheses by tissue-specific ones as the cause of reduction in the stages of mitosis may be common for different cell populations. But polyploidy in different tissues may have a different meaning associated with the specific function of the tissue. Polyploidization, as a rule, accompanies cell differentiation.

Cell polyploidy: its relation to tissue growth and function.

The effect of cell position on cell determination was studied in mouse embryos. Embryos and parts of embryos were combined during early preimplantation development. The differentiation of cells in these composites was followed either by prelabelling some cells with tritiated thymidine or by combining cells which synthesized different electrophoretic variants of glucose phosphate isomerase. It was found that each blastomere of a 4-cell embryo could form both the trophoblast and the inner cell mass of the blastocyst. However, when blastomeres of a 4-cell embryo were placed on the outside of other 4-cell embryos then (a) they tended to form the outside layer of the blastocyst, (b) they tended to develop into the trophoblast and the yolk sac on the 10th day of pregnancy, (c) they tended not to form the coat colour of the foetus. Four- to eight-cell embryos which were completely surrounded by other blastomeres had lost the capacity to form vesicles at the blastocyst stage. We could find no evidence for the segregation of morphogenetic factors at the 4- and 8-cell stages of mouse development and concluded that at these stages cell position could determine the development of blastomeres.

The effect of spatial arrangement on cell determination during mouse development

1. Trophoblast development in utero in the first half of gestation is accompanied by a rise in the ploidy levels in giant cell nuclei. Giant cells constitute up to one-third of the trophoblast population over this period. 2. The expression of polyploidy is independent of the maternal environment; the extent of polyploidy and the degree to which trophoblast develops morphologically under various conditions appear to be related. 3. The following events are not necessary for the initiation of polyploidization in trophoblast: (a) hatching from the zona pellucida, (b) oestrogen sensitization, (c) implantation, (d) postimplantation changes in topology. 4. That earlier developmental events such as the formation of the blastocoel cavity may in some way trigger polyploidization of trophoblast is not inconsistent with the studies described.

Michael I. Sherman

Papers

The effect of spatial arrangement on cell determination during mouse development

The biochemistry of differentiation of mouse trophoblast: studies on polyploidy

The biochemistry of differentiation of mouse trophoblast: alkaline phosphatase.