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Vol. 95, Issue 16, 9072-9077, August 4, 1998

Review
 The area code hypothesis revisited: Olfactory receptors and other related transmembrane receptors may function as the last digits in a cell surface code for assembling embryos

William J. Dreyer*

Division of Biology, California Institute of Technology, Pasadena, CA 91125

Edited by Masakazu Konishi, California Institute of Technology, Pasadena, CA, and approved May 27, 1998 (received for review March 9, 1998)

Recent evidence emerging from several laboratories, integrated with new data obtained by searching the genome databases, suggests that the area code hypothesis provides a good heuristic model for explaining the remarkable specificity of cell migration and tissue assembly that occurs throughout embryogenesis. The area code hypothesis proposes that cells assemble organisms, including their brains and nervous systems, with the aid of a molecular-addressing code that functions much like the country, area, regional, and local portions of the telephone dialing system. The complexity of the information required to code cells for the construction of entire organisms is so enormous that we assume that the code must make combinatorial use of members of large multigene families. Such a system would reuse the same receptors as molecular digits in various regions of the embryo, thus greatly reducing the total number of genes required. We present the hypothesis that members of the very large families of olfactory receptors and vomeronasal receptors fulfill the criteria proposed for area code molecules and could serve as the last digits in such a code. We discuss our evidence indicating that receptors of these families are expressed in many parts of developing embryos and suggest that they play a key functional role in cell recognition and targeting not only in the olfactory system but also throughout the brain and numerous other organs as they are assembled.

*   To whom reprint requests should be addressed. e-mail: dreyer{at}caltech.edu.

Copyright © 1998 by The National Academy of Sciences  0027-8424/98/959072-6$2.00/0
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