Thomas Häder

Control of triglyceride storage by a WD40/TPR-domain protein

Obesity is a metabolic disorder related to improper control of energy uptake and expenditure, which results in excessive accumulation of body fat. Initial insights into the genetic pathways that regulate energy metabolism have been provided by a discrete number of obesity‐related genes that have been identified in mammals. Here, we report the identification of the adipose (adp) gene, the mutation of which causes obesity in Drosophila. Loss of adp activity promotes increased fat storage, which extends the lifespan of mutant flies under starvation conditions. By contrast, adp gain‐of‐function causes a specific reduction of the fat body in Drosophila. adp encodes an evolutionarily conserved WD40/tetratricopeptide‐repeat‐domain protein that is likely to represent an intermediate in a novel signalling pathway.

Mechanism and Bicoid‐dependent control of hairy stripe 7 expression in the posterior region of the Drosophila embryo

Pair‐rule gene hairy (h) expression in seven evenly spaced stripes, along the longitudinal axis of the Drosophila blastoderm embryo, is mediated by a modular array of separate stripe enhancer elements. The minimal enhancer element, which generates reporter gene expression in place of the most posterior h stripe 7 (h7‐element), contains a dense array of binding sites for factors providing the trans‐acting control of h stripe 7 expression as revealed by genetic analyses. The h7‐element mediates position‐dependent gene expression by sensing region‐specific combinations and concentrations of both the maternal homeodomain transcriptional activators, Caudal and Bicoid, and of transcriptional repressors encoded by locally expressed zygotic gap genes. Caudal and Bicoid, which form complementing concentration gradients along the longitudinal axis of the embryo, function as redundant activators, indicating that the anterior determinant Bicoid is able to activate gene expression in the most posterior region of the embryo. The spatial limits of the h stripe 7 domain are brought about by the local activities of repressors which prevent activation. The results suggest that the gradients of Bicoid and Caudal combine their activities to activate segmentation genes along the entire axis of the embryo.

Gain-of-Function Screen for Genes That Affect Drosophila Muscle Pattern Formation

This article reports the production of an EP-element insertion library with more than 3,700 unique target sites within the Drosophila melanogaster genome and its use to systematically identify genes that affect embryonic muscle pattern formation. We designed a UAS/GAL4 system to drive GAL4-responsive expression of the EP-targeted genes in developing apodeme cells to which migrating myotubes finally attach and in an intrasegmental pattern of cells that serve myotubes as a migration substrate on their way towards the apodemes. The results suggest that misexpression of more than 1.5% of the Drosophila genes can interfere with proper myotube guidance and/or muscle attachment. In addition to factors already known to participate in these processes, we identified a number of enzymes that participate in the synthesis or modification of protein carbohydrate side chains and in Ubiquitin modifications and/or the Ubiquitin-dependent degradation of proteins, suggesting that these processes are relevant for muscle pattern formation.

A cascade of transcriptional control leading to axis determination in Drosophila

embryo develops through a se- tion (7,8), thus complementing the gradient of Bicoidries of rapid syncytial nuclear divisions. The nuclei mi- (Fig. 1a).grate to the egg membrane at the periphery to form The third maternal transcription factor is the zincindividualcells.Thisformationis achievedbythemem- finger protein Hunchback, which becomes asymmetri-brane extending between the nuclei to generate a sin- callydistributedinresponseto

Receptor tyrosine kinase signaling regulates different modes of Groucho-dependent control of Dorsal.

Transcriptional control of the Drosophila terminal gap gene huckebein (hkb) depends on Torso (Tor) receptor tyrosine kinase (RTK) signaling and the Rel/NFkappaB homolog Dorsal (DI). DI acts as an intrinsic transcriptional activator in the ventral region of the embryo, but under certain conditions, such as when it is associated with the non-DNA-binding co-repressor Groucho (Gro), it is converted into a repressor. Gro is recruited to the enhancer element in the vicinity of DI by sequence-specific transcription factors such as Dead Ringer (Dri). We examined the interplay between DI, Gro and Dri on the hkb enhancer and show that when acting over a distance, Gro abolishes rather than converts DI activator function. Reducing the distance between DI- and Dri-binding sites, however, switches DI into a Gro-dependent repressor that overrides activation of transcription. Both of the distance-dependent regulatory options of Gro - quenching and silencing of transcription - are inhibited by RTK signaling. These data describe a newly identified mode of function for Gro when acting in concert with DI. RTK signaling provides a way of modulating DI function by interfering either with Gro activity or with Dri-dependent recruitment of Gro to the enhancer.