A GABAergic Maf-expressing interneuron subset regulates the speed of locomotion in Drosophila

This work was funded by grants from INSERM and a 3-year Ph.D. funding from the Association Française contre les Myopathies (AFM) for H.B (Doctoral funding n°19408) and from ANR (17-CE37-0019) for T.J.Interneurons (INs) coordinate motoneuron activity to generate appropriate patterns of muscle contractions, providing animals with the ability to adjust their body posture and to move over a range of speeds. In Drosophila larvae several IN subtypes have been morphologically described and their function well documented. However, the general lack of molecular characterization of those INs prevents the identification of evolutionary counterparts in other animals, limiting our understanding of the principles underlying neuronal circuit organization and function. Here we characterize a restricted subset of neurons in the nerve cord expressing the Maf transcription factor Traffic Jam (TJ). We found that TJ+ neurons are highly diverse and selective activation of these different subtypes disrupts larval body posture and induces specific locomotor behaviors. Finally, we show that a small subset of TJ+ GABAergic INs, singled out by the expression of a unique transcription factors code, controls larval crawling speed.Publisher PDFPeer reviewe

Coe Genes Are Expressed in Differentiating Neurons in the Central Nervous System of Protostomes

Genes of the coe (collier/olfactory/early B-cell factor) family encode Helix-Loop-Helix transcription factors that are widely conserved in metazoans and involved in many developmental processes, neurogenesis in particular. Whereas their functions during vertebrate neural tube formation have been well documented, very little is known about their expression and role during central nervous system (CNS) development in protostomes. Here we characterized the CNS expression of coe genes in the insect Drosophila melanogaster and the polychaete annelid Platynereis dumerilii, which belong to different subgroups of protostomes and show strikingly different modes of development. In the Drosophila ventral nerve cord, we found that the Collier-expressing cells form a subpopulation of interneurons with diverse molecular identities and neurotransmitter phenotypes. We also demonstrate that collier is required for the proper differentiation of some interneurons belonging to the Eve-Lateral cluster. In Platynereis dumerilii, we cloned a single coe gene, Pdu-coe, and found that it is exclusively expressed in post mitotic neural cells. Using an original technique of in silico 3D registration, we show that Pdu-coe is co-expressed with many different neuronal markers and therefore that, like in Drosophila, its expression defines a heterogeneous population of neurons with diverse molecular identities. Our detailed characterization and comparison of coe gene expression in the CNS of two distantly-related protostomes suggest conserved roles of coe genes in neuronal differentiation in this clade. As similar roles have also been observed in vertebrates, this function was probably already established in the last common ancestor of all bilaterians

Abuse of Dominance in Technology-Enabled Markets: Established Standards Reconsidered?

This paper seeks to examine whether the legal standards underpinning the application of Article 102 of the Treaty on the Functioning of the European Union (TFEU) need to be revisited in light of the alleged specificities of “technology-enabled” markets. To this end, the paper is divided in seven parts. Following this short introduction (A), the paper offers first a definition of the very notion of “technology-enabled” markets (B). Then, it questions whether competition agencies should depart from conventional enforcement techniques when reviewing conduct in fast-moving, technology-enabled markets, and follow new, expedited enforcement procedures as proposed recently by several high-ranking officials (C). After this, the paper turns to substantive issues. It begins by reviewing the intricacies of market definition and dominance in technology-enabled markets (D). It then offers some general thoughts on whether a new, general legal standard for a determination of unlawful abuse is needed in technology enabled markets (E). Finally, the paper considers six categories of abusive conduct in the high-tech sector and shows that, faced with a variety of applicable legal standards for each of them, competition agencies, courts and plaintiffs have – understandably – almost always invoked and applied the loosest possible test in support of their allegations or findings. We suggest, in turn, that under existing case-law stricter standards could and should be applied, and that this is particularly important in the context of technology-enabled markets for the simple reason that it is in these markets that the most common pitfalls and shortcomings of the EU law on abuse of a dominant position are magnified (F)

GFRα1 Is Required for Development of Distinct Subpopulations of Motoneuron

International audienceGlial cell-line derived neurotrophic factor (GDNF) and its relative neurturin (NTN) are potent trophic factors for motoneurons. They exert their biological effects by activating the RET tyrosine kinase in the presence of a glycosyl-phosphatidylinositol-linked co-receptor, either GFRα1 or GFRα2. By whole-mount in situ hybridization on embryonic mouse spinal cord, we demonstrate that whereas Ret is expressed by nearly all motoneurons, Gfra 1 and Gfra 2 exhibit complex and distinct patterns of expression. Most motoneurons purified from Gfra 1 null mutant mice had lost their responsiveness to both GDNF and NTN. However, a minority of them (∼25%) retained their ability to respond to both factors, perhaps because they express GFRα2. Surprisingly, Gfra 2 − /− motoneurons showed normal survival responses to both GDNF and NTN. Thus, GFRα1, but not GFRα2, is absolutely required for the survival response of a majority of motoneurons to both GDNF and NTN. In accordance with the phenotype of the mutant motoneurons observed in culture we found the loss of distinct groups of motoneurons, identified by several markers, in the Gfra1 − /− spinal cords but no gross defects in the Gfra2 − /− mutant. During their natural programmed cell death period, motoneurons in the Gfra1 − /− mutant mice undertook increased apoptosis. Taken together these findings support the existence of subpopulations of motoneuron with different trophic requirements, some of them being dependent on the GDNF family