The Sex Determination Gene transformer Regulates Male-Female Differences in Drosophila Body Size

Abstract

Almost all animals show sex differences in body size. For example, in Drosophila, females are larger than males. Although Drosophila is widely used as a model to study growth, the mechanisms underlying this male-female difference in size remain unclear. Here, we describe a novel role for the sex determination gene transformer (tra) in promoting female body growth. Normally, Tra is expressed only in females. We find that loss of Tra in female larvae decreases body size, while ectopic Tra expression in males increases body size. Although we find that Tra exerts autonomous effects on cell size, we also discovered that Tra expression in the fat body augments female body size in a non cell-autonomous manner. These effects of Tra do not require its only known targets doublesex and fruitless. Instead, Tra expression in the female fat body promotes growth by stimulating the secretion of insulin-like peptides from insulin producing cells in the brain. Our data suggest a model of sex-specific growth in which body size is regulated by a previously unrecognized branch of the sex determination pathway, and identify Tra as a novel link between sex and the conserved insulin signaling pathway.

Sex-lethal in neurons controls female body growth inDrosophila

“…Overall, these findings suggest that neuronal Sxl promotes female body growth independently of tra , consistent with a longstanding suggestion that SSD regulation is tra -independent [3,4,11]. However, several recent studies have reported that whole body tra mutants do show a reduced female body size when measured either as larval body mass [7] or as pupal volume [15]. This mutant phenotype may be due to cell- or tissue-autonomous effects of Sxl and tra that have been observed in several tissues and appear to operate in addition to the non-autonomous role of Sxl in neurons [8,15–17].…”

“…This demonstrates that SSD is regulated differently in larval versus imaginal tissue types. It is important to note that we and others [8,15,17,38] have shown that Sxl and Tra have additional cell/tissue-autonomous effects on growth in both tissue types and, in imaginal tissues, these likely explain the gynandromorph observations. Such a combination of cell-autonomous and non-autonomous (hormonal) mechanisms is not restricted to flies and is also important for SSD in mammals [39].…”

“…Although imaginal tissue growth at larval stages is unaffected by neuronal Sxl, the increased female size of larval tissues provides a larger store of pupal resources (nutrients and/or signalling molecules) to promote/maintain increased female growth of imaginal tissues during non-feeding pupal stages. This model summarises the results from our study and does not yet incorporate results from other studies [7,15] reporting effects of Myc or fat body Tra on systemic growth.

10.1080/19336934.2018.1502535-F0003Figure 3. Neuronal Sxl increases adult wing size in females via an effect on cell size, not cell number . Neuronal Sxl knockdown ( elav c155 > Sxl RNAi ) was performed at 29°C during larval stages, followed by a shift to 18°C until eclosion to reduce elav c155 -Gal4 activity during pupal stages (for details, see legend to Figure 1 and [8]).

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“…However, several recent studies have reported that whole body tra mutants do show a reduced female body size when measured either as larval body mass [7] or as pupal volume [15]. This mutant phenotype may be due to cell- or tissue-autonomous effects of Sxl and tra that have been observed in several tissues and appear to operate in addition to the non-autonomous role of Sxl in neurons [8,15–17]. It has also been reported that tra activity in the larval fat body non-autonomously increases female body growth [15].…”

“…This mutant phenotype may be due to cell- or tissue-autonomous effects of Sxl and tra that have been observed in several tissues and appear to operate in addition to the non-autonomous role of Sxl in neurons [8,15–17]. It has also been reported that tra activity in the larval fat body non-autonomously increases female body growth [15]. In our hands, we were unable to detect similar non-autonomous functions for either Sxl or tra manipulations in the fat body, suggesting these may depend on very specific laboratory or genetic background conditions.…”