The fruit fly Drosophila melanogaster, like other arthropods, is composed of numerous body segments. The fly has several fused head segments, three thoracic segments, eight abdominal segments, and a terminal segment at the end of the abdomen. In the adult fly, these segments are clearly unique, in that a head segment has antennae, but a thoracic segment has legs instead, and an abdominal segment has neither.
About 24 hours after fertilization, a larva appears with distinct segments. The segments all look similar, but their fates to become different adult segments is already determined. Several types of genes are expressed sequentially in the embryo to define these segments. The genes involved in each step code for transcription factors, which in turn control the synthesis of other transcription factors acting on the next set of genes. The genes expressed at the end of this cascade code for proteins that carry out the functions of the cell.
Before the egg of a fruit fly has even been fertilized, the egg's anterior (A) and posterior (P) ends can already be distinguished. During egg development, nurse cells in the mother's ovary deposit regulatory molecules into the egg. These molecules define the A-P axis of the egg and direct fly development.
Among other regulatory molecules, the mother's nurse cells deposit mRNAs transcribed from several of her genes into the egg. hunchback mRNA is evenly distributed along the egg. However, the bicoid mRNA localizes to the anterior end, while the nanos mRNA localizes to the egg's posterior end.
These mRNAs are essential for normal head, thorax, and abdominal development. For example, a larva develops abnormally if the mother fruit fly had a mutation in her bicoid gene. This larva develops abdominal segments at its anterior and posterior end and lacks head and thoracic segments.
Because these mRNAs were transcribed in the mother's cells, the genes encoding them are called maternal effect genes. The maternal effect genes are the first in a series that regulate early pattern formation in the Drosophila embryo.
After a normal egg is fertilized and laid, its nucleus begins to divide. During the early divisions, the embryo translates the maternal effect mRNAs into proteins. At this point, the embryo has not yet partitioned into separate cells, so the proteins can diffuse freely to form concentration gradients.
The protein gradients are important because they regulate the embryo's own developmental genes. A number of genes control the fly's segmentation pattern. These so-called segmentation genes operate in stages. Bicoid and Nanos proteins regulate genes in the first stage: the gap genes.
hunchback is a maternal effect and a gap gene. hunchback is initially evenly distributed in the embryo, but the actions of Bicoid and Nanos establish a gradient of Hunchback protein, which then determines the anterior and posterior ends of the embryo. Nanos inhibits the translation of hunchback mRNA, thus preventing Hunchback protein accumulation at the posterior end. Meanwhile, at the anterior end, Bicoid stimulates increased transcription of the hunchback gene. This increases the amount of hunchback mRNA and protein at the anterior end, further strengthening the Hunchback gradient.
Around this time in fly development, the embryo's nuclei have migrated to the periphery.
The Hunchback protein is a transcription factor that turns on other gap genes in a concentration-dependent manner. For example, at mid-range concentrations of the Hunchback protein, a gap gene called Krüppel becomes expressed.
In addition to Krüppel, a number of other gap genes become activated in the embryo, defining large areas along the embryo's anteroposterior axis. The gap genes encode transcription factors that regulate the expression of another class of genes, called the pair rule genes.
The pair rule genes are expressed in stripes along the embryo, dividing the embryo into units of two body segments each. Many of these genes encode transcription factors, which control the expression of another class of genes, called the segment polarity genes.
The segment polarity genes are the last set of segmentation genes to turn on in the Drosophila embryo. The segment polarity genes become activated in a complex striped pattern that foreshadows the segmented body plan of the adult. Note that cell membranes begin to form around the nuclei during this time in development. By the end of this cascade, nuclei throughout the embryo "know" which segment they will be part of in the adult fly.
The next set of genes in the cascade—the Hox genes—determines the form and function of each segment. These genes are grouped in the Antennapedia cluster and the Bithorax cluster. Hox genes encode a family of transcription factors that are expressed in different combinations along the length of the embryo, and help determine cell fate within each segment.
How do we know that Hox genes determine segment identity? An important clue came from a number of bizarre mutations observed in Drosophila. One mutation occurred in the Antennapedia gene. Normally this gene is expressed in thoracic segments where legs will later develop. In the mutant, however, the gene is misexpressed in the head. The misexpression causes part of the head to take on a thoracic identity, with the development of legs in the place of antennae.
A female fly provides her eggs with the first signals that direct the process of embryo development. These signals include mRNA molecules from the maternal effect genes bicoid and nanos.
The maternal products trigger a cascade of reactions in which the embyro's own genes become activated. Classes of genes are turned on sequentially, beginning with the gap genes, which define large regions of the embryo; then with the pair rule genes, which identify smaller regions; and finally with the segment polarity genes, which define single body segments.
The Hox genes become activated at the end of this cascade and provide the individual body segments with their ultimate identity. Hox genes instruct the segments to develop according to their positions along the embryo, such that a head segment develops antennae and a thoracic segment develops legs. Mutations in Hox genes cause fascinating body transformations. For example, the Hox gene Antennapedia can mutate so that legs, rather than antennae sprout from the fly's head.
We can learn a lot about development by studying the fruit fly. Although the details may vary, the types of genes and developmental processes in fruit flies have much in common with the genes and developmental processes in other organisms, including humans.