The Developmental Strategy of Competitive Displacements and the Role of β₂-Microglobulin-H-2 or HLA Dimers in Organogenesis

Abstract

The dominant role that plasma membrane components play in cell-cell interaction, and hence organogenesis, has long been suspected. Yet, at present, testis-organizing H-Y antigen constitutes the only example of a plasma membrane component to which a specific organogenesis function has been assigned. Accordingly, the significance of this antigen extends beyond its testis-organizing function, for it serves as a model for all other organogenesis-directing antigens that will be found in the future. No biological system can be error-free. Accordingly, accidental mishaps are bound to occur at various stages of development in embryos. Natural selection must have included various accommodations to either negate or minimize the effects of these mishaps as parts of the mammalian embryonic plan. It would be an ultimate folly, for example, to assign the task of being a primordium of one entire cell type to a single early embryonic cell, for the accidental death of that cell deprives an individual entirely of one particular cell type. Wisely, each developmental commitment in mammalian development is made by a group of cells and not by a single cell (McLaren, 1976). Similarly, accidental mix-ups between differently committed cells are bound to occur at territorial boundaries during the act of organogenesis. What if the diverticulum of a primitive gut, destined to be liver, accidentally incorporated a number of stray cells that had already made an initial commitment to be intestinal cells. Purely autonomous organogenesis by irreversibly committed individual cells would have produced an island of intestinal structure in the midst of liver. The very fact that such a mosaic organ is seldom, if ever, seen indicates the existence of a developmental strategy that avoids the formation of mosaic organs. A study on the fate of XX/XY mosaic or chimeric gonads reveals the nature of this developmental strategy, which is based on the principle of competitive displacements.