The biology and evolution of the Dilp8-Lgr3 pathway: A relaxin-like pathway coupling tissue growth and developmental timing control

Author(s)

Gontijo, Alisson M. ^[1] ; Garelli, Andres ^{[1, 2, 3]}

Affiliation

^[1] Univ Nova Lisboa, Fac Ciencias Med, NOVA Med Sch, Integrat Biomed Lab, CEDOC, Chron Dis Res Ctr, Lisbon - Portugal

^[2] Univ Nacl Sur, CONICET, Inst Invest Bioquim Bahia Blanca INIBIBB, Camino La Carrindanga Km7, Bahia Blanca, Buenos Aires - Argentina

^[3] Univ Nacl Sur, Dept Biol Bioquim & Farm, Camino La Carrindanga Km7, Bahia Blanca, Buenos Aires - Argentina

• Document type: Review article
• Source: MECHANISMS OF DEVELOPMENT; v. 154, p. 44-50, DEC 2018.
• Web of Science Citations: 3

Abstract

Many insects, like cockroaches, moths, and flies, can regenerate tissues by extending the growth-competent phases of their life cycle. The molecular and cellular players mediating this coordination between tissue growth and developmental timing have been recently discovered in Drosophila. The insulin/relaxin-like peptide, Dilp8, was identified as a factor communicating abnormal growth status of Drosophila larval imaginal discs to the neuroendocrine centers that control the timing of the onset of metamorphosis. Dilp8 requires a neuronal relaxin receptor for this function, the Leucine rich repeat containing G protein coupled receptor, Lgr3. A review of current data supports a model where imaginal disc-derived Dilp8 acts on four central nervous system Lgr3-positive neurons to activate cyclic-AMP signaling in an Lgr3-dependent manner. This causes a reduction in ecdysone hormone production by the larval endocrine prothoracic gland, which leads to a delay in the onset of metamorphosis and a simultaneous slowing down in the growth rates of healthy imaginal tissues, promoting the generation of proportionate individuals. We discuss reports indicating that the Dilp8-Lgr3 pathway might have other functions at different life history stages, which remain to be elucidated, and review molecular evolution data on invertebrate genes related to the relaxin-pathway. The strong conservation of the relaxin pathway throughout animal evolution contrasts with instances of its complete loss in some clades, such as lepidopterans, which must coordinate growth and developmental timing using another mechanism. Research into these areas should generate exciting new insights into the biology of growth coordination, the evolution of the relaxin signaling pathway, and likely reveal unforeseen functions in other developmental stages. (AU)

• FAPESP's process: 16/09659-3 - Molecular physiology and evolution of a new developmental stability pathway
• Grantee: Tatiana Teixeira Torres
• Support Opportunities: Regular Research Grants