TY - JOUR
T1 - The Corazonin-PTTH Neuronal Axis Controls Systemic Body Growth by Regulating Basal Ecdysteroid Biosynthesis in Drosophila melanogaster
AU - Imura, Eisuke
AU - Shimada-Niwa, Yuko
AU - Nishimura, Takashi
AU - Hückesfeld, Sebastian
AU - Schlegel, Philipp
AU - Ohhara, Yuya
AU - Kondo, Shu
AU - Tanimoto, Hiromu
AU - Cardona, Albert
AU - Pankratz, Michael J.
AU - Niwa, Ryusuke
N1 - Funding Information:
We thank Reiko Kise, Casey Schneider-Mizell, Akira Fushiki, and Tom Kazimiers for technical assistance. We also thank Pierre Leopold and Nuria Romero for providing anti-PTTH antibody. We are grateful to all members of the Niwa laboratory for insightful discussions and comments on the manuscript. We thank Hubert Amrein, Yoshi Aso, Barry Dickson, Yoshiki Hayashi, Satoru Kobayashi, Megha, Michael B. O’Connor, Jae H. Park, Kim F. Rewitz, Jan A. Veenstra, Naoki Yamanaka, Kweon Yu, Christian Wegener, Shigeo Hayashi, the Bloomington Drosophila Stock Center, the Drosophila Genetics Resource Center, the Janelia Research Campus, the National Institute of Genetics, and the Vienna Drosophila RNAi Center for providing Drosophila stocks and reagents. E.I. was a recipient of a fellowship from the Japan Society for the Promotion of Science (JSPS) ( KAKENHI 17J00218 ). This work was supported by grants from MEXT/JSPS KAKENHI 16H04792 (R.N.); 17K19433 and 17H03658 (T.N.); 26250001 , 25890003 , 26120705 , 26119503 , 15K14307 , 16H01496 , and 17H05545 (H.T.); 17H01378 (H.T. and S.K.); Grant-in-Aid for Scientific Research on Innovative Areas ( Comprehensive Brain Science Network ; H.T.); the Naito Foundation (H.T. and Y.S.-N.); the Inoue Foundation (Y.S.-N.); the Tomizawa Jun-ichi & Keiko Fund of the Molecular Biology Society of Japan for Young Scientists (Y.S.-N.); and Deutsche Forschugnsgemeinschaft (M.J.P.). We would like to thank Editage ( https://www.editage.com ) for English language editing.
Funding Information:
We thank Reiko Kise, Casey Schneider-Mizell, Akira Fushiki, and Tom Kazimiers for technical assistance. We also thank Pierre Leopold and Nuria Romero for providing anti-PTTH antibody. We are grateful to all members of the Niwa laboratory for insightful discussions and comments on the manuscript. We thank Hubert Amrein, Yoshi Aso, Barry Dickson, Yoshiki Hayashi, Satoru Kobayashi, Megha, Michael B. O'Connor, Jae H. Park, Kim F. Rewitz, Jan A. Veenstra, Naoki Yamanaka, Kweon Yu, Christian Wegener, Shigeo Hayashi, the Bloomington Drosophila Stock Center, the Drosophila Genetics Resource Center, the Janelia Research Campus, the National Institute of Genetics, and the Vienna Drosophila RNAi Center for providing Drosophila stocks and reagents. E.I. was a recipient of a fellowship from the Japan Society for the Promotion of Science (JSPS) (KAKENHI 17J00218). This work was supported by grants from MEXT/JSPS KAKENHI 16H04792 (R.N.); 17K19433 and 17H03658 (T.N.); 26250001, 25890003, 26120705, 26119503, 15K14307, 16H01496, and17H05545 (H.T.); 17H01378 (H.T. and S.K.); Grant-in-Aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network; H.T.); the Naito Foundation (H.T. and Y.S.-N.); the Inoue Foundation (Y.S.-N.); the Tomizawa Jun-ichi & Keiko Fund of the Molecular Biology Society of Japan for Young Scientists (Y.S.-N.); and Deutsche Forschugnsgemeinschaft (M.J.P.). We would like to thank Editage (https://www.editage.com) for English language editing. E.I. Y.S.-N. and R.N. designed the experiments. E.I. T.N. Y.O. S.K. and H.T. performed the experiments and generated fly strains. E.I. S.H. P.S. A.C. and M.J.P. performed the connectome analysis. E.I. wrote the original draft. E.I. Y.S.-N. and R.N. wrote, edited, and reviewed the manuscript. The authors declare no competing interests.
Publisher Copyright:
© 2020 The Author(s)
PY - 2020/6/8
Y1 - 2020/6/8
N2 - 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.
AB - 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.
KW - bantam
KW - corazonin
KW - Drosophila
KW - ecdysteroid
KW - GnRH
KW - maturation
KW - octopamine
KW - prothoracic gland
KW - PTTH
KW - systemic growth
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U2 - 10.1016/j.cub.2020.03.050
DO - 10.1016/j.cub.2020.03.050
M3 - Article
C2 - 32386525
AN - SCOPUS:85085762593
SN - 0960-9822
VL - 30
SP - 2156-2165.e5
JO - Current Biology
JF - Current Biology
IS - 11
ER -