Dilp8 requires the neuronal relaxin receptor Lgr3 to couple growth to developmental timing.

Autor: Garelli A; 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., Heredia F; 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., Casimiro AP; 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., Macedo A; 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., Nunes C; 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., Garcez M; 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., Dias ARM; 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., Volonte YA; Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), CONICET and Universidad Nacional del Sur, Camino La Carrindanga km7, Bahía Blanca B8000 FWB, Argentina., Uhlmann T; Dualsystems Biotech AG, Grabenstrasse 11a, Schlieren CH-8952, Switzerland., Caparros E; Departamento de Medicina Clínica, Facultad de Medicina, Universidad Miguel Hernández, Ctra. Alicante-Valencia, km 87, San Juan, Alicante 03550, Spain., Koyama T; Development, Evolution and the Environment Laboratory, Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, Oeiras 2780-156, Portugal., Gontijo AM; 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.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2015 Oct 29; Vol. 6, pp. 8732. Date of Electronic Publication: 2015 Oct 29.
DOI: 10.1038/ncomms9732
Abstrakt: 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.
Databáze: MEDLINE
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