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In the previous lecture we covered the Drosophila life cycle from developing oocyte to the newly-cellularized blastoderm. At this stage (left), the embryo is shaped like a slightly bent rugby ball with about 6000 cells distributed around the surface. There are very few recognizable surface or internal features, but the future body plan is already mapped out through the expression of a set of genes known as the segmentation genes. This expression pattern - which defines a series of 15 stripes around the embryo - is a "molecular blueprint" that specifies the larval and adult segments. In this lecture we learn about the molecular events that subdivide the embryo into stripes (known as parasegments in the embryo). The key players in this process were identified during a genetic screen that was carried out by Christiane Nusslein-Volhart, Eric Wieschaus and their collaborators. Their groundbreaking effort was rewarded in 1995 by the award of the Nobel prize in Physiology and Medicine, which they shared with Ed Lewis for his work on homeotic mutants (next lecture). All animals, whether flies or humans, are constructed according to a fundamental repeated pattern so this work in Drosophila lays the foundation for understanding development of all animals.
The main player in the anterior group is bicoid, mRNA for which is localized at the anterior end of the oocyte and is translated into protein (a homeodomain transcription factor) that diffuses posteriorly to set up an anterior-posterior (high-low) concentration gradient. This serves as a morphogen gradient that helps to specify positional information along the AP-axis. The other members of the anterior group genes (e.g. exuperantia and swallow) are required to localize bicoid mRNA at the anterior pole - by binding the 3'-UTR of the mRNA. The main player in the posterior group is nanos, which forms a posterior-anterior (high-low) gradient of protein by a similar mechanism involving other members of the group such as oskar and staufen. The protein product of nanos is NOT a transcription factor but works by inhibiting the translation of mRNA encoding a homeodomain transcription factor hunchback in the posterior region (so setting up a gradient of hunchback which acts as a morphogen in the posterior part of the embryo).
2. The gap genes are activated in broad domains along the A-P axis by different concentrations of the polarity gene products. The gap genes include hunchback, kruppel and knirps, which define relatively broad regions of the embryo - two to four future segments. If a gap gene is mutated (inactivated), the corresponding broad region of the embryo does not develop and a "gap" in the pattern results. The Gap genes encode transcription factors of the zinc-finger class. They are expressed in relatively broad bands in the embryo, the boundaries of which are "sharpened" by regulatory interactions among the gap genes themselves as well as with the maternal effect genes (see above). Furthermore, the gap genes regulate the next lower group of gene in the hiearchy, the pair-rule genes (see below).
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