Microtubule-associated protein 6 mediates neuronal connectivity through Semaphorin 3E-dependent signalling for axonal growth.

Structural microtubule associated proteins (MAPs) stabilize microtubules, a property that was thought to be essential for development, maintenance and function of neuronal circuits. However, deletion of the structural MAPs in mice does not lead to major neurodevelopment defects. Here we demonstrate a role for MAP6 in brain wiring that is independent of microtubule binding. We find that MAP6 deletion disrupts brain connectivity and is associated with a lack of post-commissural fornix fibres. MAP6 contributes to fornix development by regulating axonal elongation induced by Semaphorin 3E. We show that MAP6 acts downstream of receptor activation through a mechanism that requires a proline-rich domain distinct from its microtubule-stabilizing domains. We also show that MAP6 directly binds to SH3 domain proteins known to be involved in neurite extension and semaphorin function. We conclude that MAP6 is critical to interface guidance molecules with intracellular signalling effectors during the development of cerebral axon tracts

An MRI-based classification scheme to predict passive access of 5 to 50-nm large nanoparticles to tumors

Nanoparticles are useful tools in oncology because of their capacity to passively accumulate in tumors in particular via the enhanced permeability and retention (EPR) effect. However, the importance and reliability of this effect remains controversial and quite often unpredictable. In this preclinical study, we used optical imaging to detect the accumulation of three types of fluorescent nanoparticles in eight different subcutaneous and orthotopic tumor models, and dynamic contrast-enhanced and vessel size index Magnetic Resonance Imaging (MRI) to measure the functional parameters of these tumors. The results demonstrate that the permeability and blood volume fraction determined by MRI are useful parameters for predicting the capacity of a tumor to accumulate nanoparticles. Translated to a clinical situation, this strategy could help anticipate the EPR effect of a particular tumor and thus its accessibility to nanomedicines

The use of Theranostic Gadolinium-based Nanoprobes to Improve Radiotherapy Efficacy.

International audienceUltrasmall gadolinium-based nanoparticles (GBN, hydrodynamic diameter < 5 nm) were recently developped. Since they are designed for combining renal clearance, magnetic resonance imaging (MRI) and radiosensitization, these nanoparticles appear as attractive agents for image-guidedradiotherapy. Their efficiency to improve the survival time of tumor bearing animals rests on the possibility to determine, from the data collected by MRI, the delay between the irradiation and the intravenous injection of GBN. The attempts to determine this delay were assessed by combining MRT experiments in parallel with MRI and it provided unexpected results. In this talk, we will summarize these results that were achieved through the long term project MD606 (ANR Theraguima) at the ESRF including survival curves of animals as a function of (i) the time delay between injection and irradiation, (ii) the combination between nanoparticles and temozolomide and (iii) the comparison with the radiosensitization issued by the use of Gd chelates instead of GBN. Additionally, the biodistribution of the GBN within the tumor will be presented through MRI results and XRF results (ID21). On going experiments are now focused on the comparison between the efficiency of the GBN using MRT and in parallel a 6MeV irradiator at the local hospital

The use of Theranostic Gadolinium-based Nanoprobes to Improve Radiotherapy Efficacy.

International audienceUltrasmall gadolinium-based nanoparticles (GBN, hydrodynamic diameter < 5 nm) were recently developped. Since they are designed for combining renal clearance, magnetic resonance imaging (MRI) and radiosensitization, these nanoparticles appear as attractive agents for image-guidedradiotherapy. Their efficiency to improve the survival time of tumor bearing animals rests on the possibility to determine, from the data collected by MRI, the delay between the irradiation and the intravenous injection of GBN. The attempts to determine this delay were assessed by combining MRT experiments in parallel with MRI and it provided unexpected results. In this talk, we will summarize these results that were achieved through the long term project MD606 (ANR Theraguima) at the ESRF including survival curves of animals as a function of (i) the time delay between injection and irradiation, (ii) the combination between nanoparticles and temozolomide and (iii) the comparison with the radiosensitization issued by the use of Gd chelates instead of GBN. Additionally, the biodistribution of the GBN within the tumor will be presented through MRI results and XRF results (ID21). On going experiments are now focused on the comparison between the efficiency of the GBN using MRT and in parallel a 6MeV irradiator at the local hospital