The Molecular Metamorphosis Review of Experimental Embryology

considered the central issue of developmental biology. Most embryologists have been drawn to the field by the Whether studied at the tissue, cell, or molecular level, beauty of the developing embryo and the mystery of progress requires reliable knowledge of two closely reits structure emerging from a single fertilized egg. The lated topics: the fate map of the embryo and the cell classic publications in the field of experimental embryollineage of single precursor cells. Fate maps are depicogy illustrate the power of describing cell behavior (cf. tions of what cells in various regions of an embryo will lineages, movements) and perturbing the embryo to test become during normal development. Cell lineage studhypotheses of the underlying mechanisms. This tight ies can identify the range of phenotypes that arise from coupling between observation, hypothesis, and pertursingle cells. Construction of a fate map requires a means bation has extracted significant insights from relatively of following a cell (or distinct group of cells) from a simple experimental designs. For example, by analyzing defined region of the embryo, and scoring the final pheeggs that had been fertilized by more than one sperm, notypes and positions of their progeny. In some cases, Boveri showed the importance of a full set of chromothe embryo provides a unique cellular marker, in the somes to normal development and thus established the form of a cytoplasmic inclusion (e.g., the yellow crescent chromosomes as the source of genetic material (Boveri, of some ascidian embryos) that eases this challenging 1907). Simple perturbation experiments designed to detask. In other cases, the experimental embryologist must stroy the genetic information offered some of the first introduce a label to follow a cell lineage or construct a evidence that information in the chromosomes defate map. The approaches for labeling cell lineages and pended on intact DNA (Boveri, 1904). Thus, the basic their relative merits are well defined (Fraser, 1992). While approach of the experimental embryologist—an integranone of the techniques offer all of the desired attributes tive cycle between description, proposal, and experi(neutrality, indelibility, and targeting ability), they each mentation—has generated insights that are amazing in have offered windows into the cell lineages that contheir accuracy and depth. struct the embryo. Although fate maps offer critical inforThe explosion of progress in the fields of cell biology, mation, it is important to keep in mind what a fate map biochemistry, and molecular biology has offered new or cell lineage study cannot tell us. They show the fate motivations and new technologies with which to explore of the cells if left in their context in a normal embryo, developmental mechanisms. The integrative approach which is not the same as what the cells are specified of experimental embryology offered the perfect completo become. For example, it is possible that the cells ment to these reductionistic fields, fueling rapid proghave little or no information about their eventual fate ress. As a result, embryology has recaptured its cutting but are carried by morphogenetic movements to the edge status, which many argued had been lost. In conposition where a specific instruction is provided. Simitrast to the overly etched “black/white” statements in larly, cell lineage analyses demonstrate what phenotype which a single molecule or mechanism (e.g., the only a cell adopted, not the full range of phenotypes it is one that could then be studied by that laboratory) drives capable of achieving. Although maps cannot by themall of development, the field is no longer satisfied with selves tell us whether cells are committed to generate simple-minded, linear, and absolute pathways. Now it a given tissue or cell type, fate maps are the critical first is phrasing its questions in shades of gray, asking how step in analyzing the mechanisms of cell fate determinathe many different influences on a given developmental tion, embryonic induction, and tissue morphogenesis. event are integrated to give appropriate developmental In the absence of direct evidence concerning cell linpatterning. The major challenge for the next decade eages and movement, workers sometimes substitute a will be to develop even more powerful tools for asking “molecular fate map,” the set of cells that express a questions and collecting data in a fashion that fully emgene characteristic of a later differentiated cell type or braces the complexity of the intact system. of a distinct region of the later embryo. Space does not It is, admittedly, impossible for any article or two (see allow a detailed treatment of the huge number of cases Scott, 2000) to review all of the progress in developin which such analyses have been misleading. In virtually mental biology. Rather than attempt an encyclopedic every instance, detailed examination of expression dooverview of even a narrowly prescribed subarea, we mains show only rough correspondence to the fate map. will draw examples from a few of the areas in which Cells from inside the marker gene expression domain experimental embryology has recently advanced. This