Dilp8 requires the neuronal relaxin receptor Lgr3 to couple growth to developmental timing.
How different organs in the body sense growth perturbations in distant tissues to coordinate their size during development is poorly understood. Here we mutate an invertebrate orphan relaxin receptor gene, the Drosophila Leucine-rich repeat-containing G protein-coupled receptor 3 (Lgr3), and find body asymmetries similar to those found in insulin-like peptide 8 (dilp8) mutants, which fail to coordinate growth with developmental timing. Indeed, mutation or RNA intereference (RNAi) against Lgr3 suppresses the delay in pupariation induced by imaginal disc growth perturbation or ectopic Dilp8 expression. By tagging endogenous Lgr3 and performing cell type-specific RNAi, we map this Lgr3 activity to a new subset of CNS neurons, four of which are a pair of bilateral pars intercerebralis Lgr3-positive (PIL) neurons that respond specifically to ectopic Dilp8 by increasing cAMP-dependent signalling. Our work sheds new light on the function and evolution of relaxin receptors and reveals a novel neuroendocrine circuit responsive to growth aberrations.
Integrative Biomedicine Laboratory, CEDOC-Chronic Diseases Research Center, NOVA Medical School | Faculdade de Ciencias Medicas, NOVA University of Lisbon, Campus do IGC, Rua da Quinta Grande, 6, Oeiras 2780-156, Portugal.|Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), CONICET and Universidad Nacional del Sur, Camino La Carrindanga km7, Bahía Blanca B8000 FWB, Argentina.
Andres
http://orcid.org/0000-0001-7023-0117
A
Garelli
Integrative Biomedicine Laboratory, CEDOC-Chronic Diseases Research Center, NOVA Medical School | Faculdade de Ciencias Medicas, NOVA University of Lisbon, Campus do IGC, Rua da Quinta Grande, 6, Oeiras 2780-156, Portugal.
Fabiana
F
Heredia
Integrative Biomedicine Laboratory, CEDOC-Chronic Diseases Research Center, NOVA Medical School | Faculdade de Ciencias Medicas, NOVA University of Lisbon, Campus do IGC, Rua da Quinta Grande, 6, Oeiras 2780-156, Portugal.
Andreia P
AP
Casimiro
Integrative Biomedicine Laboratory, CEDOC-Chronic Diseases Research Center, NOVA Medical School | Faculdade de Ciencias Medicas, NOVA University of Lisbon, Campus do IGC, Rua da Quinta Grande, 6, Oeiras 2780-156, Portugal.
Andre
http://orcid.org/0000-0001-6985-4520
A
Macedo
Integrative Biomedicine Laboratory, CEDOC-Chronic Diseases Research Center, NOVA Medical School | Faculdade de Ciencias Medicas, NOVA University of Lisbon, Campus do IGC, Rua da Quinta Grande, 6, Oeiras 2780-156, Portugal.
Catarina
C
Nunes
Integrative Biomedicine Laboratory, CEDOC-Chronic Diseases Research Center, NOVA Medical School | Faculdade de Ciencias Medicas, NOVA University of Lisbon, Campus do IGC, Rua da Quinta Grande, 6, Oeiras 2780-156, Portugal.
Marcia
M
Garcez
Integrative Biomedicine Laboratory, CEDOC-Chronic Diseases Research Center, NOVA Medical School | Faculdade de Ciencias Medicas, NOVA University of Lisbon, Campus do IGC, Rua da Quinta Grande, 6, Oeiras 2780-156, Portugal.
Angela R Mantas
ARM
Dias
Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), CONICET and Universidad Nacional del Sur, Camino La Carrindanga km7, Bahía Blanca B8000 FWB, Argentina.
Yanel A
http://orcid.org/0000-0002-1214-2562
YA
Volonte
Dualsystems Biotech AG, Grabenstrasse 11a, Schlieren CH-8952, Switzerland.
Thomas
T
Uhlmann
Departamento de Medicina Clínica, Facultad de Medicina, Universidad Miguel Hernández, Ctra. Alicante-Valencia, km 87, San Juan, Alicante 03550, Spain.
Esther
E
Caparros
Development, Evolution and the Environment Laboratory, Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, Oeiras 2780-156, Portugal.
Takashi
T
Koyama
Integrative Biomedicine Laboratory, CEDOC-Chronic Diseases Research Center, NOVA Medical School | Faculdade de Ciencias Medicas, NOVA University of Lisbon, Campus do IGC, Rua da Quinta Grande, 6, Oeiras 2780-156, Portugal.
Alisson M
http://orcid.org/0000-0002-2530-3708
AM
Gontijo
D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D060227:Imaginal Discs / Q000254:growth & development / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012065:Relaxin / Q000378:metabolism; D015398:Signal Transduction
D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000603337:Lgr3 protein, Drosophila; D043562:Receptors, G-Protein-Coupled; C572149:insulin-like peptide 8, Drosophila; D012065:Relaxin; D000242:Cyclic AMP