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Abstract:
The rise of developmental biology to the fore of modern biology can be traced back to the efforts of three people: Ed Lewis, Christiane Nüsslein-Volhard, and Eric Wieschaus. Lewis had been studying the homeotic Bithorax gene complex in fruitfly (Drosophila melanogaster) for several decades and came to the conclusion that the genes in this complex control body pattern along the anterior-posterior axis (7). This seminal insight, published in 1978, was followed 2 years later by another landmark publication in which Nüsslein-Volhard and Wieschaus described the results of a mutant screen from which they had isolated several classes of mutations that affected specific elements of the larval body pattern (14). Previous to this work it was generally believed that most developmental regulators would control a wide spectrum of activities, and that disrupting their function would lead to pleiotropic phenotypes that would be very difficult to interpret. With the development of recombinant DNA techniques around the same time, it took only a few years until many of the genes identified by Lewis, Nüsslein-Volhard, and Wieschaus could be studied at the molecular level. One of the first lessons was that many of the early acting genes encode transcription factors that are part of a network of regulatory interactions. For example, the maternal morphogen BICOID, a homeodomain protein, activates the zygotic gap geneHUNCHBACK, which encodes a zinc finger factor. Gap proteins, which are expressed in broad domains, in turn regulate pair rule genes, which are expressed in periodic stripes. Gap and pair rule proteins are required for region-specific expression of homeotic genes such asULTRABITHORAX and ANTENNAPEDIA, founding members of the homeobox family of transcriptional regulators. In addition to hierarchical interactions, there are also many cross-regulatory and autoregulatory interactions among gap, pair-rule, and homeotic genes. It is intriguing that although much has been learned about the regulation of the regulators, the question of how homeotic proteins subsequently specify position-dependent elaboration of different organs has largely remained a mystery.
