Functional analysis of enhancer elements regulating the expression of the Drosophila homeodomain transcription factor DRx by gene targeting.

BACKGROUND: The Drosophila brain is an ideal model system to study stem cells, here called neuroblasts, and the generation of neural lineages. Many transcriptional activators are involved in formation of the brain during the development of Drosophila melanogaster. The transcription factor Drosophila Retinal homeobox (DRx), a member of the 57B homeobox gene cluster, is also one of these factors for brain development. RESULTS: In this study a detailed expression analysis of DRx in different developmental stages was conducted. We show that DRx is expressed in the embryonic brain in the protocerebrum, in the larval brain in the DM and DL lineages, the medulla and the lobula complex and in the central complex of the adult brain. We generated a DRx enhancer trap strain by gene targeting and reintegration of Gal4, which mimics the endogenous expression of DRx. With the help of eight existing enhancer-Gal4 strains and one made by our group, we mapped various enhancers necessary for the expression of DRx during all stages of brain development from the embryo to the adult. We made an analysis of some larger enhancer regions by gene targeting. Deletion of three of these enhancers showing the most prominent expression patterns in the brain resulted in specific temporal and spatial loss of DRx expression in defined brain structures. CONCLUSION: Our data show that DRx is expressed in specific neuroblasts and defined neural lineages and suggest that DRx is another important factor for Drosophila brain development.

Polymorphisms in the IGF1 signalling pathway including the myostatin gene are associated with left ventricular mass in male athletes.

BACKGROUND: Athlete's heart as an adaptation to long-time and intensive endurance training can vary considerably between individuals. Genetic polymorphisms in the cardiological relevant insulin-like growth factor 1 (IGF1) signalling pathway seem to have an essential influence on the extent of physiological hypertrophy. OBJECTIVE: Analysis of polymorphisms in the genes of IGF1, IGF1 receptor (IGF1R) and the negative regulator of the cardiac IGF1 signalling pathway, myostatin (MSTN), and their relation to left ventricular mass (LVM) of endurance athletes. METHODS: In 110 elite endurance athletes or athletes with a high amount of endurance training (75 males and 35 females) and 27 male controls, which were examined by echocardiographic imaging methods and ergometric exercise-testing, the genotypes of a cytosine-adenine repeat polymorphism in the promoter region of the IGF1 gene and a G/A substitution at position 3174 in the IGF1R gene were determined. Additionally, a mutation screen of the MSTN gene was performed. RESULTS: The polymorphisms in the IGF1 and the IGF1R gene showed a significant relation to the LVM for male (IGF1: p=0.003; IGF1R: p=0.01), but not for female athletes. The same applies to a previously unnoticed polymorphism in the 1 intron of the MSTN gene, whose deletion allele (AAA→AA) appears to increase the myostatic effect (p=0.015). Moreover, combinations of the polymorphisms showed significant synergistic effects on the LVM of the male athletes. CONCLUSIONS: The authors' results argue for the importance of polymorphisms in the IGF1 signalling pathway in combination with MSTN on the variant degree of physiological hypertrophy of male athletes.