Abstract
SummaryThe primitive endoderm epithelial structure in mouse blastocysts forms following cell differentiation and subsequent sorting, and this two-step process can be reproduced in vitro using an embryoid body model. We found that in the chimeric embryoid bodies consisting of paired wildtype and E-cadherin null ES cells, the wildtype sorted to the center and were enveloped by the less adhesive E-cadherin null cells, in accord with Steinberg's hypothesis. However, wildtype and N-cadherin null ES cells intermixed and did not segregate, a situation that may be explained by Albert Harris' modified principle, which incorporates the unique properties of living cells. Furthermore, in chimeric embryoid bodies composed of N-cadherin and E-cadherin null ES cells, the two weakly interacting cell types segregated but did not envelop one another. Lastly, the most consistent and striking observation was that differentiated cells sorted to the surface and formed an enveloping layer, regardless of the relative cell adhesive affinity of any cell combination, supporting the hypothesis that the ability of the differentiated cells to establish apical polarity is the determining factor in surface sorting and positioning.
Highlights
The groundbreaking work of Townes and Holtfreter in 1955 demystified the patterning of embryonic cells in the spontaneous morphogenesis of germ layers, and most importantly, paved the way to a new era in the study of embryology (Townes and Holtfreter, 1955; Steinberg and Gilbert, 2004)
We found that in the chimeric embryoid bodies consisting of paired wildtype and E-cadherin null embryonic stem (ES) cells, the wildtype sorted to the center and were enveloped by the less adhesive E-cadherin null cells, in accord with Steinberg’s hypothesis
Wildtype and N-cadherin null ES cells intermixed and did not segregate, a situation that may be explained by Albert Harris’ modified principle, which incorporates the unique properties of living cells
Summary
The groundbreaking work of Townes and Holtfreter in 1955 demystified the patterning of embryonic cells in the spontaneous morphogenesis of germ layers, and most importantly, paved the way to a new era in the study of embryology (Townes and Holtfreter, 1955; Steinberg and Gilbert, 2004). Embryoid bodies mimic the early steps of spontaneous cell differentiation and morphogenesis of the early embryos and are tractable models to study these processes (Coucouvanis and Martin, 1995; Capo-Chichi et al, 2005) Such cell aggregates are popular models to explore the principles and mechanisms governing the cell sorting and positioning behaviors by developmental biologists and by mathematic modeling analysis (Armstrong et al, 2006; Brodland and Chen, 2000; Peifer, 1998; Tepass et al, 2002; Foty and Steinberg, 2005; Gumbiner, 1996; Gumbiner, 2005). Harris provided a critique of the Steinberg hypothesis, pointing out properties of living cells may cause deviations from the rule of differential adhesive affinity in some circumstances (Harris, 1976)
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