RNA-seq Analysis of Spinal Cord Tissues after Brachial Plexus Root Avulsion in Mice

Background Brachial plexus root avulsion (BPRA) can cause motor neuron death, nerve degeneration andupper limb motor dysfunction. The molecular mechanisms of motor neuron death and nerve degeneration arelargely unknown and there are no effective therapies to increase the functional recovery after BRPA.Aim: To detect the early pathway changes in spinal cord tissues after brachial plexus root avulsion.Methods A mouse brachial plexus avulsion and re-implantation model was constructed, and the C5-C7segments of the spinal cords were dissected three days after the surgery. We used RNA-seq to identify theexpression changes of genes and gene networks in spinal cord tissues.Results A total of 2253 differentially expressed genes were found significantly changed with 1852 upregulatedand 401 downregulated at 3 days after BPRA. Gene ontology (GO) enrichment analysis showed thatdifferentially expressed genes were most enriched in immune system process, regulation of immune systemprocess, defense response, plasma membrane part, extracellular region part, cell surface, protein binding,receptor binding, glycosaminoglycan binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathwayanalysis showed that the most enriched pathways included osteoclast differentiation, NF-kappa B, cytokinecytokine receptor interaction, TNF, hematopoietic cell lineage, complement and coagulation cascades, PI3KAkt, ECM-receptor interaction, NOD-like receptor, Toll-like receptor signaling pathway.Conclusions This study systematically identified the critical genes and signaling pathways in BPRA pathology.These results expand our understanding of the complex molecular mechanisms involved in BPRA and provide afoundation for future research of spinal cord tissue injury and repair.

Celsr3 is required in mouse hippocampal intrinsic wiring and spatial learning

Background The atypical cadherin Celsr3, which belongs to the core planar cell polarity group, orchestratesaxonal guidance and network wiring. Previous work using regional inactivation of Celsr3 in forebrain showedthat Celsr3 is widely involved in hippocampal maturation and connectivity. However, inactivation in the wholeforebrain does not provide sufficient specificity to address the function of Celsr3 in detail.Method We studied the Celsr3|Emx1 mouse mutant model, in which Celsr3 is selectively inactivated inhippocampal projection neurons, but not in entorhinal cortex, basal ganglia and interneurons.Result In that mutant, the hippocampal cytoarchitecture was almost normal. Inactivation of Celsr3 inprojection neurons perturbed intrinsic hippocampal wiring. Consistent with wiring defects, Celsr3|Emx1mutant mice showed impaired learning and memory, and were less anxiety-prone than control mice.Conclusion Celsr3|Emx1 mutant mice provide a simple way to study the consequences of defectivehippocampal wiring in absence of drastic structural anomalies.