Abstract
Steroid hormones are crucial for many biological events in multicellular organisms. In insects, the principal steroid hormones are ecdysteroids, which play essential roles in regulating molting and metamorphosis. During larval and pupal development, ecdysteroids are synthesized in the prothoracic gland (PG) from dietary cholesterol via a series of hydroxylation and oxidation steps. The expression of all but one of the known ecdysteroid biosynthetic enzymes is restricted to the PG, but the transcriptional regulatory networks responsible for generating such exquisite tissue-specific regulation is only beginning to be elucidated. Here, we report identification and characterization of the C2H2-type zinc finger transcription factor Ouija board (Ouib) necessary for ecdysteroid production in the PG in the fruit fly Drosophila melanogaster. Expression of ouib is predominantly limited to the PG, and genetic null mutants of ouib result in larval developmental arrest that can be rescued by administrating an active ecdysteroid. Interestingly, ouib mutant animals exhibit a strong reduction in the expression of one ecdysteroid biosynthetic enzyme, spookier. Using a cell culture-based luciferase reporter assay, Ouib protein stimulates transcription of spok by binding to a specific ~15 bp response element in the spok PG enhancer element. Most remarkable, the developmental arrest phenotype of ouib mutants is rescued by over-expression of a functionally-equivalent paralog of spookier. These observations imply that the main biological function of Ouib is to specifically regulate spookier transcription during Drosophila development.
Highlights
Steroid hormones are responsible for the coordination and regulation of many biological events during development of multicellular organisms
We show that a novel zinc finger transcription factor Ouija board (Ouib) is essential for activating the expression of one ecdysteroid biosynthesis gene, spookier, in the ecdysteroid producing cells
These results suggest that ouib may be involved in ecdysteroid biosynthesis
Summary
Steroid hormones are responsible for the coordination and regulation of many biological events during development of multicellular organisms. An important condition for achieving tissue-specificity of steroid biosynthesis is providing a regulatory mechanism that ensures tissue-specific expression of the steroidogenic enzyme genes. Major sites of steroid hormone biosynthesis are the adrenal cortex, gonads and placenta, that express steroidogenic enzyme genes such as Cyp11a1, P450c17a, 3β-HSD and 17β-HSD [1]. A collective body of previous studies has established that Ad4BP/SF-1 controls steroid hormone biosynthesis through the transcriptional regulation of all steroidogenic genes [3,5]. Forced expression of this gene is sufficient to differentiate embryonic stem cells and human induced pluripotent stem cells into the steroidogenic cells [6,7] and to induce ectopic adrenal formation [8], indicating that Ad4BP/SF-1 acts as a master regulator for steroid hormone biosynthesis in vertebrates
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