Hunting for the Genes Behind Pattern Formation
in Drosophila's Early Embryonic Development

Working together at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, Christiane Nüsslein-Volhard and Eric F. Wieschaus decided to find out how segmentation is controlled by genes in the newly fertilized egg of the Drosophila fruit fly. Their experimental strategy was unique and well planned. They treated Drosophila females with chemicals which damaged their genes and caused random mutations. They reasoned that since genes control embryonic development it should be possible to see the genetic damages as defects in the offspring and thus identify genes that specify segmentation. Studying genes intentionally damaged by mutation was the only accessible way to obtain knowledge about genes controlling development. By disturbing the system and looking for what happens you may be able to learn something about it.

Christiane Nüsslein-Volhard and Eric F. Wieschaus studied about 40 000 mutations and were able to identify 15 different genes that control the early phase of Drosophila's embryonic development (through continued research additional such genes have been found and today they are about 25). These genes caused defective segmentation when mutated, resulting e.g. in a reduced number of segments, in embryos consisting only of odd-or even-numbered segments or in segments with their head and tail ends looking similar.

Much of the embryonic development is controlled by the egg's own genes. They are divided into three functional groups which act as follows:

• The gap-genes lay the foundations of a rough body plan along the head-to-tail axis,
• the pair rule-genes govern formation of every second body segment,
• the segment polarity-genes refine the head-to-tail polarity of each individual segment, meaning that the head-end and the tail-end of a segment look different.

The three types of genes reflect a gradual refinement of Drosophila's developmental program. They come in three waves, one after the other - and it is a quick work, everything happens within hours!

Nüsslein-Volhard and Wieschaus published their important results 1980 in Nature. Their publication has had an enormous impact on how genes that control development are studied today. The paper is consequently regarded as a milestone in developmental biology.