Département de Biologie

Sensory maps, such as the representation of mouse facial whiskers, are conveyed throughout the nervous system by topographic axonal projections that preserve neighboring relationships between adjacent neurons [1]. In particular, the map transfer to the neocortex is ensured by thalamocortical axons (TCAs), whose terminals are topographically organized in response to intrinsic cortical signals [2–5]. However, TCAs already show a topographic order early in development, as they navigate toward their target [6, 7]. Here, we show that this preordering of TCAs is required for the transfer of the whisker map to the neocortex. Using Ebf1 conditional inactivation that specifically perturbs the development of an intermediate target, the basal ganglia, we scrambled TCA topography en route to the neocortex without affecting the thalamus or neocortex. Notably, embryonic somatosensory TCAs were shifted toward the visual cortex and showed a substantial intermixing along their trajectory. Somatosensory TCAs rewired postnatally to reach the somatosensory cortex but failed to form a topo- graphic anatomical or functional map. Our study reveals that sensory map transfer relies not only on positional information in the projecting and target structures but also on preordering of axons along their trajectory, thereby opening novel perspectives on brain wiring.

The multiprotein exon junction complex (EJC), deposited by the splicing machinery, is an important constituent of messenger ribonu- cleoprotein particles because it participates to numerous steps of the mRNA lifecycle from splicing to surveillance via nonsense-mediated mRNA decay pathway. By an unknown mechanism, the EJC also stimulates translation efficiency of newly synthesized mRNAs. Here, we show that among the four EJC core components, the RNA-binding protein metastatic lymph node 51 (MLN51) is a translation enhancer. Overexpression of MLN51 preferentially increased the translation of intron-containing reporters via the EJC, whereas silencing MLN51 decreased translation. In addition, modulation of the MLN51 level in cell-free translational extracts confirmed its direct role in protein synthesis. Immunoprecipitations indicated that MLN51 associates with translation-initiating factors and ribosomal subunits, and in vitro binding assays revealed that MLN51, alone or as part of the EJC, interacts directly with the pivotal eukaryotic translation initiation factor eIF3. Taken together, our data define MLN51 as a translation activator linking the EJC and the translation machinery.

N-methyl-D-aspartate receptors (NMDARs), neuronal glutamate-gated ion channels, are obligatory heterotetramers composed of GluN1 and GluN2 subunits. Each subunit contains two extracellular clamshell-like domains with an agonist-binding domain and a distal N-terminal domain (NTD). The GluN2 NTDs form mobile regulatory domains. In contrast, the dynamics of GluN1 NTD and its contribution to NMDAR function remain poorly understood. Here we show that GluN1 NTD is neither static nor functionally silent. Perturbing the conformation of GluN1 NTD affects both receptor gating and pharmacological properties. GluN1 NTD undergoes structural rearrangements that involve hinge bending and large twisting and untwisting motions, allowing for new intra- and intersubunit contacts. GluN1 NTD acts in trans with GluN2 NTD to influence binding of glutamate but, notably, not of GluN1 coagonist glycine. Our work uncovers a dynamic role of GluN1 NTD in controlling NMDAR function through new interdomain allosteric interactions.

Cell division in photosynthetic organisms is tightly regulated by light, although little is known about the cellular signaling cascades connecting light perception to cell cycle activation and progression. Here, we demonstrate that diatom-specific cyclin 2 (dsCYC2) in Phaeodactylum tricornutum displays a transcriptional peak within 15 min after light exposure, long before the onset of cell division. Transcriptional induction of dsCYC2 is triggered by the blue light sensor AUREOCHROME1a, which functions synergistically with the basic leucine zipper (bZIP) transcription factor bZIP10 to induce dsCYC2 transcription. The functional characterization of a cyclin whose transcription is controlled by light and whose activity connects light signaling to cell cycle progression contributes significantly to our understanding of the molecular mechanisms underlying light-dependent cell cycle onset in diatoms.