Journal Article

Transcriptional Control of Steroid Biosynthesis Genes in the Drosophila Prothoracic Gland by Ventral Veins Lacking and Knirps

丹羽 隆介, Moeller Morten E., Dorry Elad, Rewitz Kim F., Komura-Kawa Tatsuya, Herder Rachel, Niwa Ryusuke, Danielsen E. Thomas, Fujimoto Yoshinori, O'Connor Michael B., Troelsen Jesper T.

2014

Overview

Specialized endocrine cells produce and release steroid hormones that govern development, metabolism and reproduction. In order to synthesize steroids, all the genes in the biosynthetic pathway must be coordinately turned on in steroidogenic cells. In Drosophila, the steroid producing endocrine cells are located in the prothoracic gland (PG) that releases the steroid hormone ecdysone. The transcriptional regulatory network that specifies the unique PG specific expression pattern of the ecdysone biosynthetic genes remains unknown. Here, we show that two transcription factors, the POU-domain Ventral veins lacking (Vvl) and the nuclear receptor Knirps (Kni), have essential roles in the PG during larval development. Vvl is highly expressed in the PG during embryogenesis and is enriched in the gland during larval development, suggesting that Vvl might function as a master transcriptional regulator in this tissue. Vvl and Kni bind to PG specific cis-regulatory elements that are required for expression of the ecdysone biosynthetic genes. Knock down of either vvl or kni in the PG results in a larval developmental arrest due to failure in ecdysone production. Furthermore, Vvl and Kni are also required for maintenance of TOR/S6K and prothoracicotropic hormone (PTTH) signaling in the PG, two major pathways that control ecdysone biosynthesis and PG cell growth. We also show that the transcriptional regulator, Molting defective (Mld), controls early biosynthetic pathway steps. Our data show that Vvl and Kni directly regulate ecdysone biosynthesis by transcriptional control of biosynthetic gene expression and indirectly by affecting PTTH and TOR/S6K signaling. This provides new insight into the regulatory network of transcription factors involved in the coordinated regulation of steroidogenic cell specific transcription, and identifies a new function of Vvl and Knirps in endocrine cells during post-embryonic development.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Binding Sites / Biological Transport - genetics / Biology and Life Sciences / Biosynthesis / Cell growth / Cholesterol / Cholesterol - metabolism / DNA-Binding Proteins / Drosophila / Drosophila melanogaster - embryology / Drosophila melanogaster - genetics / Drosophila Proteins - biosynthesis / Drosophila Proteins - genetics / Drosophila Proteins - metabolism / Ecdysone / Ecdysone - biosynthesis / Ecdysone - genetics / Ecdysone - metabolism / Enzymes / Experiments / Gene expression / Gene Expression Regulation / Gene Expression Regulation, Developmental / Genetic aspects / Genetic transcription / Hormones / Insect Hormones - biosynthesis / Insect Hormones - metabolism / Insects / Membrane Proteins - biosynthesis / Microscopy / Nuclear Proteins - metabolism / Physiological aspects / POU Domain Factors - biosynthesis / POU Domain Factors - genetics / POU Domain Factors - metabolism / Repressor Proteins - biosynthesis / Repressor Proteins - genetics / Repressor Proteins - metabolism / Research and Analysis Methods / Ribosomal Protein S6 Kinases, 70-kDa - biosynthesis / RNA Interference / RNA, Small Interfering / Steroid hormones / Technological change / TOR Serine-Threonine Kinases - biosynthesis / Transcription factors / Transcription, Genetic