complishment in gene regulation, entailing a complex orchestration of which cells will express which genes when and where in the embryo and fetus. Two major elements in that regulation are (1) a large variety of specific transcription factors that act in an even larger variety of combinations to control differential gene expression; and (2) the chemical communication between cells during development that allows cells to turn specific genes on and off in response to signals from their neighbors.

The following is now realized:

  • Embryonic and fetal development involves repeated signaling among groups of cells, and the expression of particular genes in a cell depends on signaling inputs from other cells in the local environment.

  • The number of signaling pathways used in development is limited. About 17 signaling pathways are now recognized, and probably only a few more remain to be discovered. Each pathway consists of an intercellular chemical signal, a specific receptor on or within the cell, and a set of molecular transducers that transmit each signal to targets, such as to components of the transcription machinery, within the cell. These 17 pathways are used repeatedly at different times and places in the developing embryo and fetus. The roles of these pathways in development are a major focus of current research in developmental biology.

  • Surprisingly, given the morphological diversity of animal embryos and fetuses, the 17 signaling pathways are highly conserved across numerous animal phyla (e.g., nematode worms to arthropods to chordates). The molecular targets and responses within cells also are conserved across phyla, including specific gene expression, cell migration, and cell proliferation. Those signaling and responding aspects of development presumably were already present in the pre-Cambrian common ancestor of animals of modern phyla as diverse as the chordates (including humans), the arthropods (including fruit flies), and the nematodes. The differences in the development of various organisms mostly reflect differences in the particular times, places, and combinations of use of the conserved pathways and responses.

Those findings give new validity to the use of model organisms to learn more about basic development in mammals, to provide mechanistic clues about human variability, and to analyze and assess the risks of potential developmental toxicants.

With the transformation of developmental biology in the past decade, DNA sequence data from a variety of organisms have accumulated at an explosive rate. The large-scale projects initiated under the Human Genome Project include the complete sequencing of the genomes of several widely used model organisms, such as yeast, the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, the laboratory mouse, and humans. The sequencing of the yeast, C. elegans, and Drosophilia genomes has already been completed (Goffeau et al.

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