Mechanisms of growth and homeostasis in the Drosophila wing.

Animal shape and size is controlled with amazing precision during development. External factors such as nutrient availability and crowding can alter overall animal size, but individual body parts scale reproducibly to match the body even with challenges from a changing environment. How is such precision achieved? Here, we review selected research from the last few years in Drosophila--arguably the premier genetic model for the study of animal growth--that sheds light on how body and tissue size are regulated by forces intrinsic to individual organs. We focus on two topics currently under intense study: the influence of pattern regulators on organ and tissue growth and the role of local competitive interactions between cells in tissue homeostasis and final size.

Male courtship song drives escape responses that are suppressed for successful mating.

Persuasion is a crucial component of the courtship ritual needed to overcome contact aversion. In fruit flies, it is well established that the male courtship song prompts receptivity in female flies, in part by causing sexually mature females to slow down and pause, allowing copulation. Whether the above receptivity behaviours require the suppression of contact avoidance or escape remains unknown. Here we show, through genetic manipulation of neurons we identified as required for female receptivity, that male song induces avoidance/escape responses that are suppressed in wild type flies. First, we show that silencing 70A09 neurons leads to an increase in escape, as females increase their walking speed during courtship together with an increase in jumping and a reduction in pausing. The increase in escape response is specific to courtship, as escape to a looming threat is not intensified. Activation of 70A09 neurons leads to pausing, confirming the role of these neurons in escape modulation. Finally, we show that the escape displays by the female result from the presence of a courting male and more specifically from the song produced by a courting male. Our results suggest that courtship song has a dual role, promoting both escape and pause in females and that escape is suppressed by the activity of 70A09 neurons, allowing mating to occur.

apterous Brain Neurons Control Receptivity to Male Courtship in Drosophila Melanogaster Females.

Courtship behaviours allow animals to interact and display their qualities before committing to reproduction. In fly courtship, the female decides whether or not to mate and is thought to display receptivity by slowing down to accept the male. Very little is known on the neuronal brain circuitry controlling female receptivity. Here we use genetic manipulation and behavioural studies to identify a novel set of neurons in the brain that controls sexual receptivity in the female without triggering the postmating response. We show that these neurons, defined by the expression of the transcription factor apterous, affect the modulation of female walking speed during courtship. Interestingly, we found that the apterous neurons required for female receptivity are neither doublesex nor fruitless positive suggesting that apterous neurons are not specified by the sex-determination cascade. Overall, these findings identify a neuronal substrate underlying female response to courtship and highlight the central role of walking speed in the receptivity behaviour.

Evidence for a growth-stabilizing regulatory feedback mechanism between Myc and Yorkie, the Drosophila homolog of Yap.

An understanding of how animal size is controlled requires knowledge of how positive and negative growth regulatory signals are balanced and integrated within cells. Here we demonstrate that the activities of the conserved growth-promoting transcription factor Myc and the tumor-suppressing Hippo pathway are codependent during growth of Drosophila imaginal discs. We find that Yorkie (Yki), the Drosophila homolog of the Hippo pathway transducer, Yap, regulates the transcription of Myc, and that Myc functions as a critical cellular growth effector of the pathway. We demonstrate that in turn, Myc regulates the expression of Yki as a function of its own cellular level, such that high levels of Myc repress Yki expression through both transcriptional and posttranscriptional mechanisms. We propose that the codependent regulatory relationship functionally coordinates the cellular activities of Yki and Myc and provides a mechanism of growth control that regulates organ size and has broad implications for cancer.

X-ray crystallographic studies of two transthyretin variants: further insights into amyloidogenesis.

Transthyretin (TTR) is a homotetrameric plasma protein that, as a result of a set of not yet fully characterized conformational changes, forms fibrillar aggregates that are the major protein component of amyloid deposits. More than 80 mutations associated with TTR amyloid deposition have been described in the literature. X-ray crystallography was used to elucidate the three-dimensional structure of two important TTR variants: TTR Y78F, an amyloidogenic protein, and TTR R104H, which is associated with a protective effect over the amyloidogenic V30M mutation. The structures of those two TTR variants have been determined in space group P2(1)2(1)2 to 1.55 and 1.60 angstroms resolution, respectively, using molecular-replacement techniques. Detailed analysis of the protein model for TTR Y78F indicates a destabilization of the contacts between the alpha-helix and AB loop and the body of the molecule, intimately related to the amyloidogenic nature; contrastingly, in the TTR R104H variant new contacts involving the N-terminal region and His104 are clearly antagonists of amyloid formation.