title: Drosophila 4EHP is essential for the larval-pupal transition and required in the prothoracic gland for ecdysone biosynthesis.
abstract: Maternal expression of the translational regulator 4EHP (eIF4E-Homologous Protein) has an established role in generating protein gradients essential for specifying the Drosophila embryonic pattern. We generated a null mutation of 4EHP, which revealed for the first time that it is essential for viability and for completion of development. In fact, 4EHP null larvae, and larvae ubiquitously expressing RNAi targeting 4EHP, are developmentally delayed, fail to grow and eventually die. In addition, we found that expressing RNAi that targets 4EHP specifically in the prothoracic gland disrupted ecdysone biosynthesis, causing a block of the transition from the larval to pupal stages. This phenotype can be rescued by dietary administration of ecdysone. Consistent with this, 4EHP is highly expressed in the prothoracic gland and it is required for wild type expression levels of steroidogenic enzymes. Taken together, these results uncover a novel essential function for 4EHP in regulating ecdysone biosynthesis.
authors.affiliation: Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Via Selmi 3, Bologna, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Valzania
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Ono
authors.affiliation: Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Via Selmi 3, Bologna, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Ignesti
authors.affiliation: Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Via Selmi 3, Bologna, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cavaliere
authors.affiliation: Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Via Selmi 3, Bologna, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bernardi
authors.affiliation: Department of Biology, McGill University, Montreal, Quebec, Canada H3G 0B1; Department of Biology, Concordia University, Montreal, Quebec, Canada H4B 1R6. Electronic address: chiara.gamberi@concordia.ca.
authors.forename: Chiara
authors.initials: C
authors.lastname: Gamberi
authors.affiliation: Department of Biology, McGill University, Montreal, Quebec, Canada H3G 0B1. Electronic address: paul.lasko@mcgill.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: Lasko
authors.affiliation: Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Via Selmi 3, Bologna, Italy. Electronic address: giuseppe.gargiulo@unibo.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gargiulo
mesh_terms: D000818:Animals; D048429:Cell Size; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology*; D004440:Ecdysone / Q000096:biosynthesis*; D039561:Eukaryotic Initiation Factor-4E / Q000502:physiology*; D007814:Larva / Q000254:growth & development; D011679:Pupa / Q000254:growth & development; D034622:RNA Interference; D013909:Thorax / Q000196:embryology / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; C504669:eIF4EHP protein, Drosophila; D004440:Ecdysone
keywords: 4EHP gene; Drosophila larval development; Ecdysone biosynthesis; Prothoracic gland