Embryos are simpler than adults, and they allow us to analyze such basic processes more easily. Studies of the early Drosophila embryo, for example, were crucial to the discovery of several conserved signaling pathways, including the Wnt, Hedgehog, and Notch pathways. They also provided the key to understanding the central role of these pathways in the maintenance of normal adult human tissues and in diseases such as cancer.
In Chapter 22, we shall consider how other developmental mechanisms operate in the normal adult body, especially in tissues that are continually renewed by means of stem cells—including the gut, skin, and the hematopoietic system. But now, we must look more closely at the way in which an early embryo generates its spatial pattern of specialized cells, beginning with the transformations that create the adult body plan.
Animal development is a self-assembly process, in which the cells of the embryo become different from one another and organize themselves into increasingly complex structures. The process begins with a single large cell—the fertilized egg. This cell cleaves to form many smaller cells, producing a blastula. The blastula undergoes gastrulation to generate the three germ layers of the embryo—ectoderm, mesoderm, and endoderm—consisting of cells determined for different fates. As development continues, the cells become more and more narrowly specialized according to their locations and their interactions with one another. Through cell memory, these cell–cell interactions, even though transient, can have lasting effects on each
Figure 21–13 Patterning by sequential induction. a series of inductive interactions can generate many types of cells, starting from only a few.
cell’s internal state. Thus, a succession of simple cues that a cell receives at different times can direct it along a complex developmental pathway. At each step, the cell becomes further restricted in the range of final states open to it. The process reaches its limit when the cell differentiates to form one of the specialized cell types of the adult body.
Differences between developing cells arise in various ways and have to be properly coordinated in space. In one common strategy, initially similar cells within a group become different by exposure to different levels of an inductive signal or morphogen emanating from a source outside the group. Neighboring cells can also become different by lateral inhibition, in which a cell signals to its neighbors not to follow the same fate. These cell–cell interactions are mediated by a small number of highly conserved signaling pathways, which are used repeatedly in different organisms and at different times during development. Not all cell diversification arises by cell–cell interactions, however: daughter cells can be born different as a result of asymmetric cell division.
Regulators of transcription and chromatin structure bind to regulatory DNA and determine the fate of each cell. Differences of body plan seem to arise to a large extent from differences in the regulatory DNA associated with each gene. This DNA has a central role in defining the sequential program of development, calling genes into action at specific times and places according to the pattern of gene expression that was present in each cell at the previous developmental stage.
Development has been most thoroughly studied in a handful of model organisms. But most of the genes and mechanisms thereby identified are used in all animals and repeatedly at different stages of development. Thus, insights from worms, flies, fish, frogs, and mice deeply inform our understanding of embryology, birth defects, and adult tissue maintenance in humans.
A developing multicellular organism has to create a pattern in fields of cells where there was little or none before. Some of the early microscopists imagined the entire shape and structure of the human body to be already present in the sperm as a “homunculus,” a miniature human; after fertilization, the homunculus would simply grow and generate a full-sized human. We now know that this view is incorrect and that development is a progression from simple to complex, through a gradual refinement of an animal’s anatomy. To see how the whole sequence of events of spatial patterning and cell determination is set in train, we must return to the egg and the early embryo.
Different animals Use Different Mechanisms to establish their primary axes of polarization