The exquisitely beautiful form of a developing embryo is the result of a coordination between the driving forces of morphogenesis and the processes of cell growth, proliferation, differentiation, and death. Morphogenesis is responsible for bringing cell populations together for new inductive interactions and for building complex, three-dimensional structures such as hearts, limbs, lungs, and eyes out of simple epithelial sheets and mesenchymal cell masses. Research over the past two decades has elucidated many of the genetic pathways underlying cell division, cell fate determination, and differentiation, and has shown them to be evolutionarily conserved. A major challenge now is to explore the possibility that there is also a conserved “morphogenetic code”—a set of rules common to processes that are used repeatedly in different combinations to make functional organs. These instructions fall into two categories. First, there are basic subroutines that define essentially mechanical operations such as the packaging of cells into segments, the folding of epithelial sheets into tubes or cups, and the outgrowth of buds. Each of these modules utilizes sets of genes controlling properties such as differential cell adhesion, cell motility, cell-matrix interactions, and cytoskeletal organization.

The second category determines how these subroutines are coordinated with cell proliferation and cell fate determination. This “project management” depends on signaling centers that arise in the organ primordia or progenitor fields at positions initially determined by the primary embryonic axes. Each center is a group of cells that regulates the behavior of surrounding cells by producing positive and negative intercellular signaling molecules. Evidence is beginning to accumulate that the majority of these signaling factors are proteins encoded by a relatively small number of conserved multigene families, in particular the Fgfs, Bmps, Hedgehogs, Wnts, and Egf s. The diverse biological activities of individual ligands are regulated by antagonists, activators, or posttranslational modifiers that control, for example, the range over which the protein can function or its half-life in the environment. In addition, the signaling genes themselves are often transcriptionally regulated by positive and/or negative feedback loops. An exciting prospect for the future is the possibility of being able to compute how each of these variables, in combination with the downstream subroutines they control, ultimately affects the size, shape, and pattern of a particular organ.