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Guidance landscapes unveiled by quantitative proteomics to control reinnervation in adult visual system

ABSTRACT: Long-distance regeneration of the central nervous system (CNS) has been achieved from the eye to the brain through activation of neuronal molecular pathways or pharmacological approaches. Characterizing the mature neuronal environment is essential to understand the adult axonal guidance in order to complete the circuit reconstruction. To this end, we used mass spectrometry (MS)-based quantitative proteomics to characterize the proteomes of major nuclei of the adult visual system: suprachiasmatic nucleus (SCN), ventral and dorsal lateral geniculate nucleus (vLGN, dLGN) and superior colliculus (SCol)), as well as the optic chiasm. These analyses revealed the presence of guidance molecules and guidance-associated factors in the adult visual targets. Moreover, by performing bilateral optic nerve crush, we showed that the expression of specific proteins was significantly modulated by the injury in the visual targets, even in the ones most distal to the lesion site. On another hand, we found that the expression of guidance molecules was not modified upon injury and that regenerative axons are able to respond to guidance cues. Together, our results provide an extensive characterization of the molecular environment in intact and injured conditions.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Hesse Anne-Marie

LAB HEAD: Yohann Coute

PROVIDER: PXD029325 | Pride | 2022-10-20

REPOSITORIES: Pride

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Guidance landscapes unveiled by quantitative proteomics to control reinnervation in adult visual system.

Vilallongue Noemie N Schaeffer Julia J Hesse Anne-Marie AM Delpech Céline C Blot Béatrice B Paccard Antoine A Plissonnier Elise E Excoffier Blandine B Couté Yohann Y Belin Stephane S Nawabi Homaira H

Nature communications 20221013 1

In the injured adult central nervous system (CNS), activation of pro-growth molecular pathways in neurons leads to long-distance regeneration. However, most regenerative fibers display guidance defects, which prevent reinnervation and functional recovery. Therefore, the molecular characterization of the proper target regions of regenerative axons is essential to uncover the modalities of adult reinnervation. In this study, we use mass spectrometry (MS)-based quantitative proteomics to address th ...[more]

PMID: 36229455

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Project description:Genome-wide transcriptional profiling allows characterization of the molecular underpinnings of neocortical organization, including cortical areal specialization, laminar cell type diversity and functional anatomy. Microarray analysis of individual cortical layers across sensorimotor and association cortices in rhesus macaque demonstrated robust and specific laminar and areal molecular signatures driven by differential expression of genes associated with specialized neuronal function. Gene expression corresponding with laminar architecture was generally similar across cortical areas, although genes with robust areal patterning were often highly laminar as well, and these patterns were more highly conserved between macaque and human as compared to mouse. Layer 4 of primate primary visual cortex displayed a distinct molecular signature compared to other cortical regions, a specialization not observed in mouse. Overall, transcriptome-based relationships were strongest between proximal layers in a cortical area, and between neighboring areas along the rostrocaudal axis, reflecting in vivo cortical spatial topography and therefore a developmental imprint. Tissue from male and female monkeys (n = 2-3 animals/gender) was collected from anterior cingulate gyrus (ACG), layers 2, 3, 5, 6; orbitofrontal cortex (OFC), layers 2, 3, 5, 6; dorsolateral prefrontal cortex (DLPFC), layers 2-6; primary motor cortex (M1), layers 2, 3, 5, 6; primary somatosensory cortex (S1), layers 2-6; primary auditory cortex (A1), layers 2-6; primary visual cortex (V1), layers 2-6 including 4A, 4B, 4Calpha (4Ca), 4Cbeta (4Cb); secondary visual cortex (V2), layers 2-6; middle temporal area (MT), layers 2-6; temporal area (TE), layers 2-6; hippocampus, CA1, CA2, CA3, dentate gyrus (DG); and dorsal lateral geniculate nucleus (LGN), magnocellular, parvocellular and koniocellular divisions. Due to the limited number of samples that could be amplified concurrently, amplifications were performed in 3 batches (batches A-C, containing 102, 119 and 10 experimental samples, respectively). To control for batch effects, common RNA pool control samples were amplified and hybridized in each batch. These included LCM extracted hippocampus CA3 samples from the current study and a whole rhesus brain RNA pool (Biochain). These control samples were hybridized in 6 replicates in batch A and B and in 3 replicates in batch C (3 replicates per 96 well plate).

Dataset Information

Guidance landscapes unveiled by quantitative proteomics to control reinnervation in adult visual system

Publications

Guidance landscapes unveiled by quantitative proteomics to control reinnervation in adult visual system.

Similar Datasets

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