Mouse embryonic chimeras: tools for studying mammalian development

Abstract

Embryonic chimeras of the mouse are well-established tools for studying cell lineage and cell potential. They are also a key part of the analysis of complex phenotypes of mutant mice. By combining embryonic stem cell technology, molecularly tagged mutations and sensitive cell lineage markers,chimeras can provide invaluable insights into the tissue-specific requirement and the mode of action of many mouse genes.

Cell and molecular regulation of the mouse blastocyst

“…This extraembryonic cell population sends signals and initiates the A/P axis in the embryo. However, it is not yet understood how and when this population is specified, nor is it clear whether there is a direct relationship between these cells and any prior asymmetries-at the blastocyst stage or earlier (reviewed in Tam and Rossant, 2003;Rossant and Tam, 2004;Zernicka-Goetz, 2004).…”

Generation of human/rat xenograft animal model for the study of human donor stem cell behaviorsin vivo

“…In theory, foreign cells transplanted to embryonic environment (e.g. blastocyst and in uter o ) may be provided with all the possible lineage options available during development [16] . But as shown in Figure 2, higher levels of human cell engraftment occurred in solid organs examined, compared with blood, which was consistent with the goat results reported by Zeng et al [8] ; in addition, the chimerism was also nonuniformly distributed over all solid organs analyzed, as mentioned in mice [5,17,18] .…”

“…It is well known that multipotent adult stem/progenitor cells can in vitro and in vivo give rise to many cell types under the right conditions, while totipotent embryonic stem cells (ES cells) microinjected into blastocysts can differentiate into all tissue types in chimeras under the appropriate conditions (such as blastocyst stage) [16] . In animals and human, ES cells appear at the early developmental stage, followed by the disappearance of ES cells and the appearance of adult stem/progenitor cells.…”

“…In animals and human, ES cells appear at the early developmental stage, followed by the disappearance of ES cells and the appearance of adult stem/progenitor cells. Theoretically, foreign cells, such as ES cells and adult stem/progenitor cells, introduced to embryonic environment may be provided with all the possible lineage options available during development [16] , but the aforementioned findings seem to suggest that blastocyst stage is pretty suitable for the engraftment, survival, proliferation and differentiation of ES cells, but not adult stem/progenitor cells in allogeneic and xenogeneic recipient microenvironment because the engraftment, survival and proliferation of adult stem/progenitor cells in blastocyst might be greatly influenced by competition of endogenous ES cells in inner cell mass, whereas fetuses are capable of supporting the engraftment, survival, proliferation and differentiation of adult stem/progenitor cells in allogeneic and xenogeneic settings which may provide certain developmental cues that do not exist in embryonic stage, as supported by findings [24] .…”

Using a histone yellow fluorescent protein fusion for tagging and tracking endothelial cells in ES cells and mice

“…For example, endothelial-specific green fluorescent protein (GFP) reporters have proven useful for noninvasive observation of vascular development in zebrafish (Isogai et al, 2003;Lawson and Weinstein, 2002;Motoike et al, 2000). The uniform expression of GFP within the endothelial cells of these animals limits their utility in following cell movements: the position of a given cell can be tracked in three dimensions (3D) over time (i.e., in 4D) only if it is present among a group of nonexpressing cells, as in a mosaic or mixed-lineage population (e.g., see Anderson et al, 2000;Bak and Fraser, 2003;Hadjantonakis et al, 2001;Srinivas et al, 2004;Tam and Rossant, 2003). Ultimately, it will be desirable to construct anatomical models for analysis of normal, mutant, and pathological vascular development.…”