Connecting cell behavior to patterning: lessons from the cell cycle.

An organism is made up of a myriad of intricate structures, each with its own shape and designated place within the whole. The development of an organism thus requires the proper formation and correct positioning of each of these individual parts. Accordingly, a major focus of developmental research has been an understanding of the mechanisms underlying the establishment of positional information, which serves as the basis for both the creation of individual structures and for the correct placement of tissues within the entire organism. After many fruitful years of research into this area, many aspects of patterning are becoming clear. But positional information is an abstract code while the organism is a physical reality, the code being interpreted in the process of morphogenesis. If we are really to understand the flow of the structural information that proportions, shapes, and positions structures, we need to understand the process of interpretation of positional information. One role of positional information is the specification of the tissue-specific programs of gene expression. While tissue-specific gene expression is the major determinant of the functional specialization of different tissues, other aspects of the tissue such as size and shape are regulated differently. Consider your arm and leg: they consist of similar tissues that are organized into similar elements and laid out in an analogous fashion, yet the differences between them are profound and of obvious importance. The development of these highly related structures likely relies upon the same combination of cell behaviors, and the differences between the structures presumably reflect subtle differences in the time, magnitude, and position of these common processes. Similarly, the formation of all organs and structures of the body will rely to a major extent on the precise control of basic cellular processes such as cell movements, shape changes, and division. While these phenomena can be controlled by regulation of gene expression, the format of this regulation is different from that usually emphasized in developmental studies of tissue-specific gene expression. Morphogenesis is far too complex to study holistically, but the regulation of some of the individual cell behaviors that contribute to morphogenesis can be approached. One of the cell behaviors whose control we are beginning to understand at a molecular level is cell proliferation. The lessons learned from studies of the cell cycle are generalizable and provide a paradigm for an understanding of many aspects of cell behavior required for morphogenesis; we will discuss here the regulation of several such behaviors. There are several steps involved in the link between patterning information and cell behavior: the interpretation of complex patterning information by a regulatory factor, the transduction of a signal produced by this factor, and, finally, the regulation of specific cell biological phenomena in response to this transduction. In some cases, such as that involving the mitotic regulator Cdc25String, a single factor completes the link between patterning and cell behavior. In others, the individual steps are carried out by distinct factors, introducing increasing complexity to the link between patterning and cell behavior.