The POU Factor Ventral Veins Lacking/Drifter Directs the Timing of Metamorphosis through Ecdysteroid and Juvenile Hormone Signaling

Autor: E. Thomas Danielsen, Michael B. O'Connor, Ryusuke Niwa, Elad Dorry, Kim F. Rewitz, Morten E. Moeller, Tatsuya Komura-Kawa, Yoshinori Fujimoto, Rachel Herder, Jesper T. Troelsen
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Cancer Research
Transcription
Genetic
Gene Expression
chemistry.chemical_compound
Molecular Cell Biology
Transcriptional regulation
Morphogenesis
Drosophila Proteins
Prothoracicotropic hormone
Pattern Formation
RNA
Small Interfering
Genetics (clinical)
Regulation of gene expression
TOR Serine-Threonine Kinases
Gene Expression Regulation
Developmental
Nuclear Proteins
Ribosomal Protein S6 Kinases
70-kDa
Animal Models
Prothoracic gland
Cell biology
DNA-Binding Proteins
Cholesterol
Drosophila melanogaster
Cell Processes
Insect Hormones
RNA Interference
Ecdysone
Research Article
Signal Transduction
lcsh:QH426-470
Steroid biosynthesis
Biology
Research and Analysis Methods
Cell Growth
Molecular Genetics
Model Organisms
Genetics
Animals
Molecular Biology
Transcription factor
Ecology
Evolution
Behavior and Systematics
Binding Sites
Membrane Proteins
Biology and Life Sciences
Biological Transport
Cell Biology
Molecular biology
Repressor Proteins
lcsh:Genetics
chemistry
Nuclear receptor
Gene Expression Regulation
POU Domain Factors
Gene Function
Organism Development
Animal Genetics
Developmental Biology
Zdroj: Danielsen, E T, Møller, M E, Dorry, E, Komura-Kawa, T, Fujimoto, Y, Troelsen, J, Herder, R, O'Connor, M B, Niwa, R & Rewitz, K F 2014, ' Transcriptional control of steroid biosynthesis genes in the Drosophila prothoracic gland by Ventral veins lacking and Knirps ', P L o S Genetics, vol. 10, no. 6, e1004343 . https://doi.org/10.1371/journal.pgen.1004343
PLoS Genetics, Vol 10, Iss 6, p e1004343 (2014)
PLoS Genetics
Popis: 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.
Author Summary Steroid hormones play important roles in physiology and disease. These hormones are molecules produced and secreted by endocrine cells in the body and control sexual maturation, metabolism and reproduction. We found transcriptional regulators that underlie the specialized function of endocrine steroid-producing cells. In the steroid-producing cells of the fruit fly Drosophila, Ventral veins lacking (Vvl) and Knirps (Kni) turn on all the genes required for steroid production. When Vvl or Kni were inactivated in the cells where the hormone is made, the genes involved in steroid production were not activated. Because of the reduced steroid production, the juvenile larvae failed to develop and undergo maturation to adulthood. Inactivation of Vvl and Kni also reduces endocrine cell growth by disturbing their response to growth promoting signals. Genetic variations in humans with the loss of a homolog of Vvl have been associated with disorders caused by insufficient steroid production. Together with the fact that Vvl is highly expressed in the steroid-producing cells of Drosophila, this suggests that Vvl may be a conserved master regulator of steroid production. Our findings provide insight into the network of factors that control endocrine cell function and steroid hormone levels that could have implication for human diseases.
Databáze: OpenAIRE
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