Neural Circuits and Systems Neuroscience
Author: Andres Garelli | email: andres.garelli@gmail.com
Magdalena Fernandez Acosta 1°, Heredia Fabiana 1°, Juliane Menezes 1°, Rebeca Zanini 1°, Katja Prüger 1°, Agustina Dronseck 2°, Maite Arana 2°, Joana Pereirinha 1°, Jan Veenstra 3°, Christian Wegener 4°, Alisson Gontijo 1°*, Andrés Garelli 2°*
1° iNOVA4Health, NOVA Medical School|Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.
2° INIBIBB, Universidad Nacional del Sur-CONICET, Bahía Blanca, Argentina.
3° INCIA UMR 5287 CNRS, Université de Bordeaux, allée Geoffroy St Hillaire, Pessac, France.
4° Neurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, University of Würzburg, Würzburg, Germany.
Drosophila pupariation consists of a series of innate behaviors and morphogenetic changes that lead to the formation of a hardened pupal case (puparium) from the larval cuticle and its attachment to a substrate. The latter is achieved by the glue expulsion behavior (GSB). GSB is preceded by strong body-remodelling contractions, termed pre-GSB. The steroid hormone ecdysone coordinates the whole pupariation process, inducing initiation of pre-GSB and its progression to GSB by inducing an epidermis-to-CNS relaxin-like Dilp8-Lgr3 signaling event. The factors that induce GSB and post-GSB behaviors downstream of ecdysone remain to be defined. Here we use neuronal-specific RNAi against a series of neuropeptides to identify Myoinhibiting peptide (MIP) as a critical peptide required for GSB. In its abscence, GSB is attempted, yet it is abnormal, and glue is not expulsed. MIP acts spatially and temporally downstream of the Dilp8 pathway. Cell-type-specific MIP RNAi showed that MIP is required in a single bilateral descending brain neuron for proper GSB. Mutation of the MIP receptor Sex-peptide receptor (SPR) or RNAi of SPR in specific neurons mimics the MIP mutant phenotype, indicating that MIP acts via neuronal SPR to ensure proper GSB. Our results advance our molecular and cellular understanding of pupariation control, reveal the complexity of glue expulsion and spreading behavior control, and contribute to the understanding of how multi-step innate behaviors are coordinated in time.
*Corresponding authors: alisson.gontijo@nms.unl.pt and agarelli@inibibb-conicet.gob.ar