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Molecular physiology and evolution of a new developmental stability pathway

Grant number: 16/09659-3
Support type:Regular Research Grants
Duration: April 01, 2017 - March 31, 2019
Field of knowledge:Biological Sciences - Genetics - Animal Genetics
Principal researcher:Tatiana Teixeira Torres
Grantee:Tatiana Teixeira Torres
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Álisson Marques de Miranda Cabral Gontijo ; Andres Garelli


Developmental stability is the ability of an organism to buffer given traits against environmental and intrinsic perturbations. This may involve physiological, temporal or behavioral adjustments to the developmental program. The processes leading to developmental stability have been particularly well studied in arthropods. For instance, if uncoordinated growth is induced in the larval imaginal discs (the precursors of adult appendages) of Drosophila flies, a transient delay in the onset of metamorphosis ensues, allowing extra time for all discs to achieve their species specific size and proportion. How exactly this exquisite coordination between growth and developmental timing is achieved is not completely understood. Recently, others and us have identified a fly-specific insulin/IGF-I/relaxin peptide named Drosophila insulin-like peptide 8 (Dilp8) that responds to uncoordinated imaginal tissue growth and delays the onset of metamorphosis by inhibiting, via an unknown mechanism, the biosynthesis of the major insect molting hormone, Ecdysone. Loss of dilp8 increases intra-individual asymmetry and yields individuals with a greater than normal range of size variation and time of maturation. Thus, Dilp8 is a central player in the communication system that mediates the adjustments to promote developmental stability in Drosophila. Our preliminary molecular evolution data suggest that Dilp8 evolved in the last common ancestor to all Brachycera (flies) about 180 million years ago. How other insects, including other non-brachyceran Diptera, such as mosquitoes, communicate abnormal imaginal disc growth to the neuroendocrine centers coordinating developmental timing in the absence of a Dilp8 peptide is unknown. Also, the extent of the conservation at the molecular level between the peripheral epithelial tissue responses upstream of Dilp8 activation and the neuroendocrine responses to tissue insults downstream of Dilp8 are not clear. To start gaining insight into how this new developmental stability pathway evolved, we plan to use a combination of molecular genetics, bioinformatics, functional genomics and biochemical assays, and evo-devo approaches mainly with a nematoceran and key Brachycera flies. We hope to determine the ancestral signaling pathway that coordinated growth and developmental timing prior to the origination of Dilp8 and its function as a developmental-delay-inducing factor. Our results should provide insight into the poorly understood physiological mechanisms used for interorgan growth coordination, and maybe shed new light into the evolution of new signaling pathways. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CARDOSO, GISELE ANTONIAZZI; DESZO, MARINA SANTOS; TORRES, TATIANA TEIXEIRA. Evolution of coding sequence and gene expression of blowflies and botflies with contrasting feeding habits. Genomics, v. 113, n. 1, 2, p. 699-706, . (16/09659-3, 14/13933-8, 12/23200-2, 14/01600-4)
HEREDIA, FABIANA; VOLONTE, YANEL; PEREIRINHA, JOANA; FERNANDEZ-ACOSTA, MAGDALENA; CASIMIRO, ANDREIA P.; BELEM, CLAUDIA G.; VIEGAS, FILIPE; TANAKA, KOHTARO; MENEZES, JULIANE; ARANA, MAITE; et al. The steroid-hormone ecdysone coordinates parallel pupariation neuromotor and morphogenetic subprograms via epidermis-to-neuron Dilp8-Lgr3 signal induction. NATURE COMMUNICATIONS, v. 12, n. 1, . (16/10342-4, 17/17904-0, 16/09659-3)
GONTIJO, ALISSON M.; GARELLI, ANDRES. The biology and evolution of the Dilp8-Lgr3 pathway: A relaxin-like pathway coupling tissue growth and developmental timing control. MECHANISMS OF DEVELOPMENT, v. 154, p. 44-50, . (16/09659-3)
MACEDO, ANDRE; GONTIJO, ALISSON M.. The intersectional genetics landscape for humans. GIGASCIENCE, v. 9, n. 8, . (16/09659-3)

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