Another Written Assignment , due to be handed in next Wednesday (September 18), and which will be graded a little more critically than the first written assignment.

Please choose two of the sixteen publications mentioned below (The URLs of which are given) and succinctly summarize the content (data, argument, conclusions) of each one.

Also, please summarize the relations between your two chosen papers. Do they contradict each other? Do they support the same or different conclusions? If so, in what sense?

Your total text should be between one and two single-spaced typed pages, or the equivalent number of words if hand-written.

A Very Short History of Cell Sorting

1907: Wilson discovers that dissociated and randomly mixed sponge cells sort out (Except he concludes the cells are switching differentiated cell types, or maybe developing from archeocytes = stem cells)

1930s-50s Holtfreter discovers frog & salamander embryo cells sort out by germ layer (ectoderm, mesoderm, endoderm; and subdivisions e.g. neural vs. somatic ectoderm.) He suggests that differences in "tissue affinity " cause sorting out.

1955 Townes and Holtfreter publish the classic paper on cell sorting, which summarizes Townes nine years of PhD research.

1950s Moscona and Trinkaus (separately) demonstrate that bird and mammal embryo cells can be dissociated with proteolytic enzymes and EDTA (divalent ion chelator), and that they sort out according to differentiated cell type (heart, liver, pigmented retina) with no changing of cell type, producing spheres of one cell type surrounded by cells of another cell type.


Moscona tries to discover tissue-specific cell-cell adhesion proteins (like cadherins), but his bioassays are not specific enough. Trinkaus decides that sorting out is unimportant because it doesn't happen in normal embryos. One of Trinkaus' graduate students claims gastrulation and neurulation amount to sorting out.

1963 Malcolm Steinberg invents a way to explain sorting out based on differences in amount of adhesiveness.
[] (& many later papers)
"The Differential Adhesion Hypothesis" sometimes called The Thermodynamic Theory.

1969 Herbert Phillips compares resistance to centrifugal flattening of spheres of different cell types, & claims this is a way to measure cell-cell "work of adhesion"
Others continue similar methods []

1970 Steinberg compares inside-outside locations of sorting for about 8 differentiated cell types
All comparisons of cell types obey "transitive hierarchy"= if A inside B & B inside C: then A inside C
(This was predicted by his DAH theory.)

Meanwhile, (1970s & 80s) Gerald Edelman, M. Takiechi and others are discovering different kinds of cell-cell adhesion proteins, contrary to the DAH idea of different amounts of one kind of adhesion.

1976 Harris claims that Steinberg has misunderstood thermodynamics and that Phillips has been measuring cell contractility, instead of adhesiveness, but that these mistakes don't reduce the importance of their observations.

1994 Steinberg and Takeichi insert genes for P-Cadherin (and E-Cadherin) into cells of a tissue culture line
Those cells having the most cadherin sort out into internal spheres, relative to cells with less cadherin. Also see
[] from 1988

2002 Wayne Brodland proposes a "Differential Interfacial Tension Hypothesis"
He also has a computer simulation on line. And a good paper about "Finite Element" computer simulations of epithelia and other living tissues.

2005 Foty and Steinberg
[] Summarize the evidence from their point of view, which is that if differences in amounts of cadherins can cause sorting out, that proves other cases of sorting out are caused by differences in amount of adhesiveness.

Another interesting paper about the thermodynamics of cell adhesion: by Bell and Dembo.

And a very important paper showing that cancerous cells sort out (to the exterior position) relative to equivalent non-cancerous cells; Does this mean the cancerous cells are less adhesive, or exert weaker contractility? Or both? Or neither?)
[] Gershman, Drumm and Culp


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