| Elongation of the Drosophila embryonic hindgut epithelium occurs by a process of oriented cell rearrangement. The elongating hindgut becomes subdivided into domains—small intestine, large intestine, and rectum—each characterized by a specific pattern of gene expression. The proper specification of small intestine fate has been shown to depend on the function of three genes, drumstick (drm), bowel (bowl) and lines ( lin). The drm and bowl hindguts are short and wide and are missing the small intestine, while the lin hindgut is bloated with an expansion of small intestine fate. Understanding the genetic and biochemical interaction between these genes is the focus of this dissertation.; Using positional cloning, I have molecular characterized the drm gene and show that it encodes an 81 amino acid (10 kDa) zinc finger protein that is a member of the Odd-skipped (Odd) family of transcriptional regulators including Drm, Bowl, Odd, and Sob. lin is epistatic to drm in all tissues coexpressing these genes, including the hindgut, proventriculus, and dorsal epidermis. In the hindgut, lin is expressed broadly throughout the primordium and represses small intestine fate, while drm expression is localized to the midgut-hindgut junction and is required to establish small intestine. These results suggest a model in which localized expression of drm blocks lin activity, thereby allowing small intestine to be established. Supporting this model, ectopic expression of Drm throughout the hindgut produces a lin-like phenotype. Biochemical and genetic data indicate that the first C2H2 zinc finger of Drm is essential for Lin-binding and Lin-inhibiting activities.; bowl is expressed broadly throughout the gut primordium and is required to establish small intestine fate. bowl is epistatic to lin, suggesting a model in which lin represses small intestine fate by inhibiting bowl. Ectopic expression of Bowl throughout the hindgut does not alter cell fates, suggesting that bowl may act permissively to establish the small intestine. I have thus defined a pathway in which the spatially localized expression of Drm antagonizes the globally expressed, bowl-inhibiting Lin protein, thereby leading to specification of a domain (the small intestine) necessary for oriented cell rearrangement. |
