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Response to the Authors

Posted by PLOS_Genetics on 20 Feb 2008 at 10:44 GMT

Originally submitted as a Reader Response by Avrum Gratch ( on 12 November 2006:

In the paper, "Anatomic Demarcation by Positional Variation in Fibroblast Gene Expression Programs," you ask the question "How do cells know where they are in the body?" Your answer (if I am phrasing your view correctly) is that fibroblasts have consistent gene expression programs depending on their anatomic origin [with] several striking binary gene expression signatures that demarcated positional boundaries, and this surprisingly simple spatial organization of fibroblast differentiation is supportive of a model of patterning based on a position in a coordinate system.

Some years ago [1], I proposed a somewhat different explanation for why cells appear where they do in the developing/developed organism. The accepted view that positional gradients were determining factors seemed me to have serious logical difficulties. The question I asked was not why cells know where they are in the body, but how/why do cells end up where they do during development.

The answer I offered (perhaps not articulately enough), is that a cell ends up where it does because of a series of genetically determined developmental steps - a sequence of cell divisions - that physically places that cell in a specific location in the body. In other words, a cell does not have to "know" where it is; it is delivered to a specific location as a result of its genetically determined history, which does not require the operation of "positional information" in the usual sense of that term.

1. Gratch AV (1995) A formal description of cell lineage and a hypothesis: all cell lineages are fixed J Theor Biol 174:237-260.