Biology subjects

Noblet, V.

Publications and source records attributed to Noblet, V..

4 recordsLinked to original sources

bioRxiv2022

Ts66Yah, a refined Ts65Dn DS mouse model, unravels genetic interaction between regions homologous to Human chromosome 21 and the Scaf8-Pde10a genetic interval.

Down syndrome is caused by trisomy of human chromosome 21 (Hsa21). The understanding of phenotype-genotype relationships, the identification of driver genes and various proof-of-concepts for therapeutics have benefited from mouse models. The premier model, named Ts(1716)65Dn/J (Ts65Dn), displayed phenotypes related to the human DS features. It carries an additional minichromosome with the Mir155 to Zbtb21 region of mouse chromosome 16 (Mmu16), homologous to Hsa21, encompassing around 90 genes, fused to the centromeric part of mouse chromosome 17 (Mmu17) fromPisd-ps2/Scaf8 to Pde10a, containing 46 genes, not related to Hsa21. Here, we report the investigation of a new model, Ts66Yah, generated by CrispR/Cas9 without the genomic region unrelated to Hsa21 on the minichromosome. As expected, Ts66Yah replicated DS cognitive features. However, certain phenotypes related to increased activity, spatial learning and molecular signatures, were changed suggesting genetic interactions between the Mir155-Zbtb21 and the Scaf8-Pde10a interval. Thus, Ts66Yah mice have a stronger construct and face validity for mimicking consequences of DS genetic overdosage. Furthermore, this report is the first to demonstrate genetic interactions between triplicated regions homologous to Hsa21 and others unrelated to Hsa21.

genetics↗

bioRxiv2020

A Multicenter Preclinical MRI Study: Definition of Rat Brain Relaxometry Reference Maps

Similarly to human population imaging, there are several well-founded motivations for animal population imaging, the most notable being the improvement of the validity of statistical results by pooling a sufficient number of animal data provided by different imaging centers. In this paper, we demonstrate the feasibility of such a multicenter animal study, sharing raw data from forty rats and processing pipelines between four imaging centers. As specific use case, we considered the estimation of T1 and T2 maps for the healthy rat brain at 7T. We quantitatively report about the variability observed across two data provider centers and evaluate the influence of image processing steps on the final maps, by using three fitting algorithms from three centers. Finally, to derive relaxation time values per brain area, two multi-atlas segmentation pipelines from different centers were executed on two different platforms. In this study, the impact of the acquisition was 2.21% (not significant) and 9.52% on T1 and T2 estimates while the impact of the data processing pipeline was not significant (1.04% and 3.33%, respectively). In addition, the computed normality values can serve as relaxometry reference maps to explore differences to animal models of pathologies.

neuroscience↗

bioRxiv2019

Mapping the living mouse brain neural architecture: strain specific patterns of brain structural and functional connectivity

Mapping the structural and functional brain connectivity fingerprints became an essential approach in neurology and experimental neuroscience because network properties can underlie behavioral phenotypes. In mouse models, revealing strain related patterns of brain wiring have a tremendous importance, since these animals are used to answer questions related to neurological or neuropsychiatric disorders. C57BL/6 and BALB/cJ inbred strains are primary \"genetic backgrounds\" for brain disease modelling and for testing therapeutic approaches. Nevertheless, extensive literature describes basal differences in the behavioral, neuroanatomical and neurochemical profiles of the two strains, which raises the question whether the observed effects are pathology specific or depend on the genetic background. Here we performed a systematic comparative exploration of brain structure and function of C57BL/6 and BALB/cJ mice via Magnetic Resonance Imaging (MRI). We combined voxel-based morphometry (VBM), diffusion MRI and high resolution fiber mapping (hrFM) and resting state functional MRI (rs-fMRI) and depicted brain-wide dissimilarities in the morphology and \"connectome\" features in the two strains. Particularly C57BL/6 animals show bigger and denser frontal cortical areas, cortico-striatal tracts and thalamic and midbrain pathways, and higher density of fibers in the genu and splenium of the corpus callosum. These features are fairly reflected in the functional connectograms that emphasize differences in \"hubness\", frontal cortical and basal forbrain connectivity. We demonstrate strongly divergent reward-aversion circuitry patterns and some variations of the default mode network features. Inter-hemispherical functional connectivity showed flexibility and adjustment regarding the structural patterns in a strain specific manner. We further provide high-resolution tractograms illustrating also inter-individual variability across inter-hemispherical callosal pathways in the BALB/cJ strain.

neuroscience↗

bioRxiv2019

Rere-dependent Retinoic Acid signaling controls brain asymmetry and handedness

While the vertebrate brain appears largely bilaterally symmetrical in humans, it presents local morphological Left-Right (LR) asymmetries as, for instance, in the petalia. Moreover, higher functions such as speech or handedness are asymmetrically localized in the cortex. How these brain asymmetries are generated remains unknown. Here, we reveal a striking parallel between the control of bilateral symmetry in the brain and in the precursors of vertebrae called somites, where a \"default\" asymmetry is buffered by Retinoic Acid (RA) signaling. This mechanism is evident in zebrafish and mouse and, when perturbed in both species, it translates in the brain into lateralized alterations of patterning, neuronal differentiation and behavior. We demonstrate that altering levels of the mouse RA coactivator Rere results in subtle cortex asymmetry and profoundly altered handedness, linking patterning and function in the motor cortex. Together our data uncover a novel mechanism that could underlie the establishment of brain asymmetries and handedness in vertebrates.

neuroscience↗