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The Corazonin-PTTH Neuronal Axis Controls Systemic Body Growth by Regulating Basal Ecdysteroid Biosynthesis in Drosophila melanogaster.

  • Imura, Eisuke1
  • Shimada-Niwa, Yuko2
  • Nishimura, Takashi3
  • Hückesfeld, Sebastian4
  • Schlegel, Philipp4
  • Ohhara, Yuya5
  • Kondo, Shu6
  • Tanimoto, Hiromu7
  • Cardona, Albert8
  • Pankratz, Michael J4
  • Niwa, Ryusuke9
  • 1 Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan. , (Japan)
  • 2 Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, 305-8577 Tsukuba, Japan. Electronic address: [email protected] , (Japan)
  • 3 RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan. , (Japan)
  • 4 Department of Molecular Brain Physiology and Behavior, LIMES Institute, University of Bonn, Bonn 53115, Germany. , (Germany)
  • 5 School of Food and Nutritional Sciences, Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan. , (Japan)
  • 6 Invertebrate Genetics Laboratory, National Institute of Genetics, Mishima 411-8540, Japan. , (Japan)
  • 7 Graduate School of Life Sciences, Tohoku University, Sendai 980-8577, Japan. , (Japan)
  • 8 Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
  • 9 Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, 305-8577 Tsukuba, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan. , (Japan)
Published Article
Current biology : CB
Publication Date
Jun 08, 2020
DOI: 10.1016/j.cub.2020.03.050
PMID: 32386525


Steroid hormones play key roles in development, growth, and reproduction in various animal phyla [1]. The insect steroid hormone, ecdysteroid, coordinates growth and maturation, represented by molting and metamorphosis [2]. In Drosophila melanogaster, the prothoracicotropic hormone (PTTH)-producing neurons stimulate peak levels of ecdysteroid biosynthesis for maturation [3]. Additionally, recent studies on PTTH signaling indicated that basal levels of ecdysteroid negatively affect systemic growth prior to maturation [4-8]. However, it remains unclear how PTTH signaling is regulated for basal ecdysteroid biosynthesis. Here, we report that Corazonin (Crz)-producing neurons regulate basal ecdysteroid biosynthesis by affecting PTTH neurons. Crz belongs to gonadotropin-releasing hormone (GnRH) superfamily, implying an analogous role in growth and maturation [9]. Inhibition of Crz neuronal activity increased pupal size, whereas it hardly affected pupariation timing. This phenotype resulted from enhanced growth rate and a delay in ecdysteroid elevation during the mid-third instar larval (L3) stage. Interestingly, Crz receptor (CrzR) expression in PTTH neurons was higher during the mid- than the late-L3 stage. Silencing of CrzR in PTTH neurons increased pupal size, phenocopying the inhibition of Crz neuronal activity. When Crz neurons were optogenetically activated, a strong calcium response was observed in PTTH neurons during the mid-L3, but not the late-L3, stage. Furthermore, we found that octopamine neurons contact Crz neurons in the subesophageal zone (SEZ), transmitting signals for systemic growth. Together, our results suggest that the Crz-PTTH neuronal axis modulates ecdysteroid biosynthesis in response to octopamine, uncovering a regulatory neuroendocrine system in the developmental transition from growth to maturation. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

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