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AstA signaling functions as an evolutionary conserved mechanism timing metamorphosis and growth in Drosophila Melanogaster

Abstract : The onset of puberty occurs in response to the integration of various internal homeostatic and external signals. Up until now, it remains largely unknown which internal sensory mechanisms are involved in the coupling of those signals. In mammals, the onset of puberty is associated with elevated GnRH pulsations leading to a peak of steroid hormones. The KISS/KISSR system is a pivotal upstream regulator of GnRH producing neurons. In Drosophila melanogaster a peak of prothoracicotropic hormone (PTTH) produced by two pairs of neurons (PTTHn) leads to the production of the insect steroid hormone ecdysone. PTTH is one of the first signals to activate the cascade of events leading to maturation. Once PTTH production is blocked, a delay is observed in the onset of the transition from juvenile to adult stage, whereas precocious maturation is observed upon PTTH over-expression, denoting an important role for PTTHn in the integration of cues. In order to uncover signals integrated by PTTHn we have conducted a biased RNAi screen in PTTHn. After two rounds of screening we identified the GPCR Allatostatin A receptor 1 (AstA-R1) as a positive regulator of PTTHn. AstA-R1 knock down delays maturation with a subsequent increase in final pupal size. Down regulation of its ligand, Allatostatin-A (AstA) on the brain is also affecting the timing of maturation. We found that AstA is produced in the central brain by a bilateral pair of neurons that extend their axons towards the PTTHn dendrites. In addition, AstA neurons also project their axons towards the Drosophila insulin producing cells (IPCs) that are known to regulate larval growth. Knockdown of AstA-R1 on the IPCs leads to smaller pupae. These findings imply that the AstA neurons are able to regulate growth and maturation timing by interacting with 2 different circuits: the PTTHn and IPCs. Unexpectedly, AstA-R1 and AstA genes share a common evolutionary origin with KISSR and KISS, respectively, suggesting a common mechanism between insects and mammals for the integration of signals that control the onset of puberty.
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Derya Deveci. AstA signaling functions as an evolutionary conserved mechanism timing metamorphosis and growth in Drosophila Melanogaster. Cellular Biology. Université Côte d'Azur, 2018. English. ⟨NNT : 2018AZUR4090⟩. ⟨tel-02064973⟩

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