Autophagy in cell fate decisions: knowledge gained from Drosophila.

Autophagy is an important process that maintains adult tissue homeostasis and functions by protecting cells in autonomous and non-cell-autonomous ways. By degrading toxic components or proteins involved in cell signaling pathways, autophagy preserves the balance among stem cells, progenitors, and differentiated cells in various tissues. In this minireview, we discuss recent studies performed in Drosophila that highlight new roles of autophagy in adult cell fate decisions, including quiescence, proliferation, differentiation, and death.

The Drosophila hep pathway mediates Lrrk2-induced neurodegeneration.

Although the pathogenesis of Parkinson's disease (PD) remains unclear, mutations in leucine-rich repeat kinase 2 (Lrrk2) are among the major causes of familial PD. Most of these mutations disrupt Lrrk2 kinase and (or) GTPase domain function, resulting in neuronal degeneration. However, the signal pathways underlying Lrrk2-induced neuronal degeneration are not fully understood. There is an expanding body of evidence that suggests a link between Lrrk2 function and MAP kinase (MAPK) cascades. To further investigate this link in vivo, genetic RNAi screens of the MAPK pathways were performed in a Drosophila model to identify genetic modifier(s) that can suppress G2019S-Lrrk2-induced PD-like phenotypes. The results revealed that the knockdown of hemipterous (hep, or JNKK) increased fly survival time, improved locomotor function, and reduced loss of dopaminergic neurons in G2019S-Lrrk2 transgenic flies. Expression of the dominant-negative allele of JNK (JNK-DN), a kinase that is downstream of hep in G2019S-Lrrk2 transgenic flies, elicited a similar effect. Moreover, treatment with the JNK inhibitor SP600125 partially reversed the G2019S-Lrrk2-induced loss of dopaminergic neurons. These results indicate that the hep pathway plays an important role in Lrrk2-linked Parkinsonism in flies. These studies provide new insights into the molecular mechanisms underlying Lrrk2-linked PD pathogenesis and aid in identifying potential therapeutic targets.

[Drosophila as a model to study cancer biology]. / Le modèle drosophile et la recherche en cancérologie.

The rising global incidence of cancer makes it the second leading cause of death worldwide. Over the past decades, significant progress has been made in both basic knowledge and the discovery of new therapeutic approaches. However, the complexity of mechanisms related to tumor development requires the use of sophisticated and adapted research tools. Among these, the fruitfly Drosophila melanogaster represents a powerful genetic model with numerous practical and conceptual advantages. Indeed, the conservation of genes implicated in cancer between this insect and mammals places Drosophila as a crucial genetic tool for understanding the fundamental mechanisms governing tumorigenesis and identifying new therapeutic targets. This review aims to describe this original model and demonstrate its relevance for studying cancer biology.

[Cloning method forDrosophila cells in vitro. Sensitivity to X-rays of different cell lines]. / Méthode de clonage des cellules de drosophile. Sensibilité aux rayons X de plusieurs lignées cellulaires.

1. The sensitivity to X-rays of 5 differentDrosophila cell lines has been studied. Statistical analysis of experimental data for doses between 10,000 and 16,000 roentgen showed that, for each cell line, the probability of survial of each cell is independent. According to the relationship observed between the dose and the survival frequency, the five lines studied can be classified into 3 groups. Moreover, the cell population of each line is heterogeneous with respect to radiosensitivity, some cells being more radioresistant than others. 2. UnirradiatedDrosophila cells seeded at a very low multiplicity are unable to multiply unless they are cultured among heavily irradiated cells. Each cell has an independant probability of initiating a clone. This probability,p, is different for each one of the 3 cell lines examined:p 1=0.69,p 3=0.35,p 6=0.02. These differences are likely to have a genetic origin. 3. The ability of a single cell to initiate a clone, when cultured among cells whose multiplication has been stopped by X ray irradiation, provides a simple and efficient cloning method. The conditions in which a given cell line could be cloned were defined after determination of the dose-survival relationship and estimation ofp. The cloning procedure is described. The homogeneity of the karyotype and cell morphology can be used to monitor the homogeneity of the cell population.