Genes VII

The basic question of Drosophila development is illustrated in Figure 29.1 in terms of three stages of development: the egg; the larva; and the adult fly.

At the start of development, gradients are established in the egg along the anterior-posterior and dorsal-ventral axes. The anterior end of the egg becomes the head of the adult; the posterior end becomes the tail. The dorsal side is on top (looking down on a larva); the ventral side is underneath. The gradients consist of molecules (proteins or RNAs) that are differentially distributed in the cytoplasm. The gradient responsible for anterior-posterior development is established soon after fertilization; the dorsal-ventral gradient is established a little later. It is only a modest oversimplification to say that the anterior-posterior systems control positional information along the larva, while the dorsal-ventral system regulates tissue differentiation (that is, the specification of distinct embryonic tissues, including mesoderm, neuroectoderm, and dorsal ectoderm).

Insect development involves two quite different types of structures. The first part of development is concerned with elaborating the larva; then the larva metamorphoses into the fly. This means that the structure of the embryo (the larva) is distinct from the structure of the adult (the fly), in contrast with development of (for example) mammals, where the embryo develops the same body parts that are found in the adult. As the larva develops, it forms some body parts that are exclusively larval (they will not give rise to adult tissues; often they are polyploid), while other body parts are the progenitors that will metamorphose into adult structures (they are usually diploid). In spite of the differences between insect development and vertebrate development, the same general principles appear to govern both processes, and we discover relationships between Drosophila regulators and mammalian regulators.

Discrete regions in the embryo correspond to parts of the adult body. They are shown in terms of the superficial organization of the larva in the middle panel of Figure 29.1. Bands of denticles (small hairs) are found in a particular pattern on the surface (cuticle) of the larva. The cuticular pattern has features determined by both the anterior-posterior axis and the dorsal-ventral axis:

• Along the anterior-posterior axis, the denticles form discrete bands. Each band corresponds to a segment of the adult fly: in fact, the 11 bands of denticles correspond on a 1:1 basis with the 11 segments of the adult.
• Along the dorsal-ventral axis, the denticles that extend from the ventral surface are coarse; those that extend from the dorsal surface are much finer.

Although the cuticle represents only the surface body layer, its structure is diagnostic of the overall organization of the embryo in both axes. Much of the analysis of phenotypes of mutants in Drosophila development has therefore been performed in terms of the distortion of the denticle patterns along one axis or the other.

The difference in form between the gradients of the egg and the segments of the adult poses some prime questions. How are gradients established in the egg? And how is a continuous gradient converted into discrete differences that define individual cell types? How can a large number of separate compartments develop from a single gradient?

The nature of the gradients, and their ability to affect the development of a variety of cell types located throughout the embryo, depend upon some idiosyncratic features of Drosophila development. The early stages are summarized in Figure 29.2.

At fertilization the egg possesses the two parental nuclei and is distinguished at the posterior end by the presence of a region called polar plasm. For the first 9 divisions, the nuclei divide in the common cytoplasm. Material can diffuse in this cytoplasm (although there are probably constraints imposed by cytoskeletal organization). At division 7, some nuclei migrate into the polar plasm, where they become precursors to germ cells. After division 9, nuclei migrate and divide to form a layer at the surface of the egg. Then they divide 4 times, after which membranes surround them to form somatic cells.

Up to the point of cellularization, the nuclei effectively reside in a common cytoplasm. At the stage of the cellular blastoderm, the first discrete compartments become evident, and at this time particular regions of the egg are determined to become particular types of adult structures. (Determination is progressive and gradual; over the next few cell divisions, the fates of individual regions of the egg become increasingly restricted.) At the start of this process, nuclei migrate to the surface to form the monolayer of the blastoderm, but they do not do so in any predefined manner. It is therefore the location in which the nuclei find themselves at this stage that determines what types of cells their descendants will become. A nucleus determines its position in the embryo by reference to the anterior-posterior and dorsal-ventral gradients, and behaves accordingly.