Nuria Magdalena Romero

Steroid hormones, crucial for development and physiology, were traditionally believed to diffuse passively through membranes. However, recent evidence shows insect steroid ecdysone being secreted via regulated exocytosis, but the mechanisms ensuring successful hormone release into circulation remain unclear. Our study identifies specialized membrane protrusions, signaling filopodia, in the Drosophila prothoracic gland as essential for vesicle-mediated steroid release. Confocal imaging reveals that these actin- and tubulin-rich structures form a membrane-intertwined basal domain critical for secretion. Disrupting filopodia by interfering with basement membrane interactions—Perlecan or β-integrin—or filopodia-specific protein expression—α-actinin—significantly reduces ecdysone signaling by impairing its release, despite proper production in the gland. Additionally, filopodia dynamics, such as length and density, align with secretion timing and hormone circulating levels, suggesting their role in synchronizing release with physiological needs. The systematic presence of membrane protrusions in steroid-secreting glands across species prompts a comprehensive re-evaluation of steroid release mechanisms.

Steroid hormones, crucial for development and physiology, were traditionally believed to diffuse passively through membranes. However, recent evidence shows insect steroid ecdysone being secreted via regulated exocytosis, but the mechanisms ensuring successful hormone release into circulation remain unclear. Our study identifies specialized membrane protrusions, filopodia-like structures named "hormonemes," in the Drosophila prothoracic gland as essential for steroid vesicle release. Confocal imaging reveals that these actin- and tubulin-rich structures form a membrane-intertwined basal domain critical for secretion. Disrupting filopodia by interfering with BM interactions, perlecan or beta-integrin, or filopodia-specific protein expression, alpha-actinin, significantly reduces ecdysone signaling by impairing its release, despite proper production in the gland. Additionally, filopodia dynamics, such as length and density, align with secretion timing and hormone circulating levels, suggesting their role in synchronizing release with physiological needs. The systematic presence of membrane protrusions in steroid-secreting glands across species prompts a comprehensive re-evaluation of steroid release mechanisms.

Puberty and metamorphosis are two major developmental transitions linked to the reproductive maturation. In mammals and vertebrates, the central brain acts as a gatekeeper, timing the developmental transition through the activation of a neuroendocrine circuitry. In addition to reproduction, these neuroendocrine axes and the sustaining genetic network play additional roles in metabolism, sleep and behavior. Although neurohormonal axes regulating juvenile-adult transition have been classically considered the result of convergent evolution (i.e., analogous) between mammals and insects, recent findings challenge this idea, suggesting that at least some neuroendocrine circuits might be present in the common bilaterian ancestor Urbilateria. The initial signaling pathways that trigger the transition in different species appear to be of a single evolutionary origin and, consequently, many of the resulting functions are conserved with a few other molecular players being co-opted during evolution.

In mammals like humans, adult fitness is improved due to resource allocation, investing energy in the developmental growth process during the juvenile period, and in reproduction at the adult stage. Therefore, the attainment of their target body height/size co-occurs with the acquisition of maturation, implying a need for coordination between mechanisms that regulate organismal growth and maturation timing. Insects like Drosophila melanogaster also define their adult body size by the end of the juvenile larval period. Recent studies in the fly have shown evolutionary conservation of the regulatory pathways controlling growth and maturation, suggesting the existence of common coordinator mechanisms between them. In this review, we will present an overview of the significant advancements in the coordination mechanisms ensuring developmental robustness in Drosophila. We will include (i) the characterization of feedback mechanisms between maturation and growth hormones, (ii) the recognition of a relaxin-like peptide Dilp8 as a central processor coordinating juvenile regeneration and time of maturation, and (iii) the identification of a novel coordinator mechanism involving the AstA/KISS system.

Adult size and fitness are controlled by a combination of genetics and environmental cues. In Drosophila, growth is confined to the larval phase and final body size is impacted by the duration of this phase, which is under neuroendocrine control. The neuropeptide prothoracicotropic hormone (PTTH) has been proposed to play a central role in controlling the length of the larval phase through regulation of ecdysone production, a steroid hormone that initiates larval molting and metamorphosis. Here, we test this issue by examining the consequences of null mutations in the ptth gene on Drosophila development. Loss of ptth causes several developmental defects including a delay in developmental timing, increase in critical weight, loss of coordination between body and imaginal disc growth, and reduced adult survival in sub-optimal environmental conditions like nutrition deprivation or high population density. We show that these defects are caused by a decrease in ecdysone production associated with altered transcription of ecdysone biosynthetic genes. Therefore, the PTTH signal contributes to proper coordination between various environmental cues and the developmental program to ensure individual fitness and survival.

Autophagy is an evolutionary conserved process by which eukaryotic cells undergo self-digestion of cytoplasmic components. Here we report that a novel Drosophila immunophilin, which we have named Zonda, is critically required for starvation-induced autophagy. We show that Zonda operates at early stages of the process, specifically for Vps34-mediated phosphatidylinositol 3-phosphate (PI3P) deposition. Zonda displays an even distribution under basal conditions and, soon after starvation, nucleates in endoplasmic reticulum–associated foci that colocalize with omegasome markers. Zonda nucleation depends on Atg1, Atg13, and Atg17 but does not require Vps34, Vps15, Atg6, or Atg14. Zonda interacts physically with Atg1 through its kinase domain, as well as with Atg6 and Vps34. We propose that Zonda is an early component of the autophagy cascade necessary for Vps34-dependent PI3P deposition and omegasome formation.

Médecine/sciences (M/S), revue internationale dans le domaine de la recherche biologique, médicale et en santé

Looking for the Dark: Mature Drosophila larvae wander away from food and seek a dark site for pupation. While investigating this phenomenon Yamanaka et al. (p. 1113 ) found that four prothoracicotropic hormone (PTTH)–producing neurons mediate light preference in the central brain. PTTH circulates in the hemolymph and signals via its receptor, Torso, to two light sensors, sensitizing them for light detection. The larvae can then transform from wandering larvae into immobile pupae hidden from light and predatory eyes.