Amit Singh - Molecular Genetics of Axial Patterning, Growth and Disease in Drosophila Eye

The fly sat upon the axle tree of the chariot-wheel and said, what a dust do I raise!Aesop

The quest to understand how a single-celled embryo is transformed into a multicellular three-dimensional organism with complex structure and functions has been a challenge for the developmental biologists for ages. This question resembles the search for the holy grail of modern-day biology. During the development of a multicellular organism, cell proliferation is tightly regulated to produce specific number of cells, which in turn is followed by a fundamental process of differentiation that is regulated by a genetic circuitry. Any perturbation in this finely tuned process results in defects. Therefore, the basic cell biological process of cell proliferation, cell differentiation, and cell death play important roles in sculpting an organ during organogenesis. Since the genetic machinery is highly conserved, it has been pointed out that the basic core machinery involved in regulating these fundamental processes are similar. In developmental biology, it is important to unravel the mechanism of fate assignment and differentiation.

The time testedDrosophila melanogaster(fruit fly) model has played a central role in developmental biology during the twentieth century. TheDrosophilamodel has a long genetic legacy, beginning with Thomas Hunt Morgan in early 1900 (Morgan 1911). A judicious blend of molecular and developmental genetics has proved beyond doubt thatDrosophilais a valuable model for addressing important questions of modern-day biology. There are several thousand people whose work/lives center around the little fruit flyDrosophila melanogaster. In recent years, the emphasis of their studies has shifted from inheritance to development and disease. In the hands of a small number of particularly imaginative scientists, traditional genetics, experimental embryology, and new molecular genetic techniques have been combined to build a picture of developmental mechanisms. To date,Drosophilahas maintained its status as a trusted and highly versatile model to study patterning, growth, and disease. Among all the adult body structures, theDrosophilaeye, because of its simple structure and easy amenability to mutations and genome-wide screens has become an important tool in the hands of Drosophilists.

The study of developing eye from a two-dimensional eye primordium to a three-dimensional adult eye and visual system, and the use of eye model to study patterning, growth, development, evolution, and disease is the topic of the current book. TheDrosophilaeye has been intensively studied to explore cell biological processes like cell fate specification, patterning, growth, and cell signaling. Understanding the generation and functioning of eye as an organ, our primary sensory modality, is important. We are curious to know how the visual system assembles.

It is now almost 37 years since the seminal paper from Ready et al. (1976) described the development and structure ofDrosophilacompound eye. The discovery of morphogenetic furrow (MF), a wave of differentiation, which is initiated from the posterior margin of the eye imaginal disc and sweeps in the anterior direction (Ready et al. 1976), is considered to be a major milestone inDrosophilaeye field. It results in differentiation of retinal precursor cells to photoreceptor neurons. It was known that adult appendage develops from a group of cells set aside during embryonic development, which grows during larval stages and then metamorphose into adult appendages. Tomlinson provided the electron microscopic view of cellular events that follow the formation of morphogenetic furrow (Tomlinson 1985). Generation of monoclonal antibodies to detect early cell differentiation was another major landmark (Fujita et al. 1982). Enhancer trap technique using P element-mediated transgenesis proved to be an important tool that still remains an asset in the arsenal of modern-day fly geneticists tool kit (Bellen et al. 1989; Grossniklaus et al. 1989; Wilson et al. 1989). Another important milestone was demonstration of structural and functional similarity in the genetic circuitry involved in eye development in flies and humans (Halder et al. 1995; Quiring et al. 1994). These studies completely changed the outlook of the eye field. Halder et al. (1995) reported the master selector gene concept in the eye where they demonstrated thateyeless (ey) Drosophilahomolog of PAX-6 gene could reprogram other tissues and generate ectopic eyes in the wing, leg, and antenna. These studies provided a great impetus to theDrosophilaeye model, which by then was also used to address questions for human disease. The evolution ofDrosophilaeye research cannot be complete without mentioning the contributions of Seymour Benzer, Walter Gehring, and Gerald M. Rubin. The hard work of Gerald Rubin and his collaborators came to fruition when fly genome was published in 2000 (Adams et al. 2000; Myers et al. 2000; Rubin et al. 2000). It was instrumental in validating the observation of Gehrings group that there is a strong conservation in the genetic circuitry of flies with that of humans and other vertebrates. It completely changed the field and put the fly model on the forefront among all other animal models. These discoveries led to generation of new genetic and molecular technology, and put