Biology subjects

Grmai, L.

Publications and source records attributed to Grmai, L..

3 recordsLinked to original sources

bioRxiv2024

Sexually dimorphic ATF4 expression in the fat confers female stress tolerance in Drosophila melanogaster

Metabolic differences between males and females have been well documented across many species. However, the molecular basis of these differences and how they impact tolerance to nutrient deprivation is still under investigation. In this work, we use Drosophila melanogaster to demonstrate that sex-specific differences in fat tissue metabolism are driven, in part, by dimorphic expression of the Integrated Stress Response (ISR) transcription factor, ATF4. We found that female fat tissues have higher ATF4 activity than their male counter parts under homeostatic conditions. This dimorphism was partly due to a female bias in transcript abundance of specific ATF4 splice isoforms. We found that the canonical sex determinants transformer (tra) and doublesex (dsx) drive such dimorphic ATF4 transcript abundance. These differences persist in a genetic model of nutrient deprivation, where female animals showed greater resistance to lethality than males in an ATF4-dependent manner. These results suggest that higher ATF4 activity confers higher tolerance to stress in females. Together, our data describe a previously unknown facet of ISR signaling wherein sexual identity of adipose tissue confers differential stress tolerance in males and females. Since energy storage mechanisms are known to be dimorphic and have been linked to ATF4 regulation, our studies provide a mechanistic starting point for understanding how sexual identity influences metabolic disease outcomes.

cell biology↗

bioRxiv2023

Steroid signaling controls sex-specific development in an invertebrate

In vertebrate sexual development, two important steroid hormones, testosterone and estrogen, regulate the sex-specific development of many tissues. In contrast, invertebrates utilize a single steroid hormone, ecdysone, to regulate developmental timing in both sexes. However, here we show that in Drosophila melanogaster, sex-specific ecdysone (E) signaling controls important aspects of gonad sexual dimorphism. Rather than being regulated at the level of hormone production, hormone activity is regulated cell-autonomously through sex-specific hormone reception. Ecdysone receptor (EcR) expression is restricted to the developing ovary and is repressed in the testis at a time when ecdysone initiates ovary morphogenesis. Interestingly, EcR expression is regulated downstream of the sex determination factor Doublesex (Dsx), the founding member of the Dsx/Mab3 Related Transcription Factor (DMRT) family that regulates gonad development in all animals. E signaling is required for normal ovary development1,2, and ectopic activation of E signaling in the testis antagonized stem cell niche identity and feminized somatic support cells, which were transformed into follicle-like cells. This work demonstrates that invertebrates can also use steroid hormone signaling to control sex-specific development. Further, it may help explain recent work showing that vertebrate sexual development is surprisingly cell-autonomous. For example, chickens utilize testosterone and estrogen to control sex-specific development, but when they have a mixture of cells with male and female genotypes, the male cells develop as male and the female cells develop as female despite exposure to the same circulating hormones3. Sex-specific regulation of steroid hormone signaling may well underly such cell-autonomous sexual fate choices in vertebrates as it does in Drosophila.

developmental biology↗

bioRxiv2023

Integrated Stress Response signaling acts as a metabolic sensor in fat tissues to regulate oocyte maturation and ovulation

Reproduction is an energy-intensive process requiring systemic coordination. However, the inter-organ signaling mechanisms that relay nutrient status to modulate reproductive output are poorly understood. Here, we use Drosophila melanogaster as a model to establish the Integrated Stress response (ISR) transcription factor, Atf4, as a fat tissue metabolic sensor which instructs oogenesis. We demonstrate that Atf4 regulates the lipase Brummer to mediate yolk lipoprotein synthesis in the fat body. Depletion of Atf4 in the fat body also blunts oogenesis recovery after amino acid deprivation and re-feeding, suggestive of a nutrient sensing role for Atf4. We also discovered that Atf4 promotes secretion of a fat body-derived neuropeptide, CNMamide, which modulates neural circuits that promote egg-laying behavior (ovulation). Thus, we posit that ISR signaling in fat tissue acts as a "metabolic sensor" that instructs female reproduction: directly, by impacting yolk lipoprotein production and follicle maturation, and systemically, by regulating ovulation.

genetics↗