Project description:An exquisite example of form serving function is the dorsal horn of the spinal cord, the gateway to the central nervous system for sensory information from the body. Each sensory input to the dorsal horn targets a specific address within its laminated arrangement of diverse neuronal populations. However, it is not known how this organization emerges during development from an apparently homogenous pool of neural progenitors. Here, we found that both the excitatory and inhibitory cell families of the mouse dorsal horn were born in successive waves as temporal cohorts. The excitatory families then settled into a chronotopic map that transformed their birth order into the dorsal laminae. Diversification of families into refined neuron types was mediated by a dorsal-ventral progenitor gradient of Zic transcription factors. This work uncovered fundamental temporal and spatial factors that establish the cell types and structure of the spinal cord dorsal horn.
Project description:An exquisite example of form serving function is the dorsal horn of the spinal cord, the gateway to the central nervous system for sensory information from the body. Each sensory input to the dorsal horn targets a specific address within its laminated arrangement of diverse neuronal populations. However, it is not known how this organization emerges during development from an apparently homogenous pool of neural progenitors. Here, we found that both the excitatory and inhibitory cell families of the mouse dorsal horn were born in successive waves as temporal cohorts. The excitatory families then settled into a chronotopic map that transformed their birth order into the dorsal laminae. Diversification of families into refined neuron types was mediated by a dorsal-ventral progenitor gradient of Zic transcription factors. This work uncovered fundamental temporal and spatial factors that establish the cell types and structure of the spinal cord dorsal horn.
Project description:We generated single cell RNA-seq data to measure the transctiptional profiles of cervicothoracic human pluripotent stem cell-derived dorsal horn spheroids cultured together with human DRG spheroids in an in-vitro model of the dorsal root ganglion-spinal horn dorsal horn pain circuit. hPSC derived dorsal horn interneurons were generated using our previously established protocol and aggregated into spheroids. These spheroids were cultured in a microphysiological device for 5 weeks together with human DRG spheroids created using hiPSC derived nociceptors purchased from Anatomic Inc. In toal we recovered the transcriptomes of 28,445 cells. Analysis verified the presence of the dI4/dI5 cells of the superficial dorsal horn which are implicated in the modeled pain circuit. These cells also expressed a high level of late-born neuronal markers NFIB and Neurod2.
Project description:Here we performed a ChIP-seq experiment for Tlx3 trancription factor on a sample of mouse embryonic dorsal spinal cord. The result is the generation of the genome-wide maps for Tlx3 binding to chromatin in dILB neurones of the developing dorsal horn.
Project description:This SuperSeries is composed of the following subset Series: GSE21258: Transcript Profiling of Spinal Dorsal Horn in Response to Electroacupuncture on Rats at 1h GSE21733: Transcript Profiling of Spinal Dorsal Horn in Response to Electroacupuncture on Rats at 24h Refer to individual Series
Project description:For development of gene expression of L5 spinal tissue in SNL mice, L5 spinal nerve was first tightly ligated to construct the neuropathic pain model, and sham-operated group as a control. After chronic administrations of vehicle (distilled water, 10 mg/kg) or WTD (12.60 g/kg, p.o.), L5 spinal cord of dorsal horn were collected, and then, Agilent Whole Mouse Genome Microarray 4×44K expression profiling were employed as a discovery platform to identify genes with the potential to provide basis for the clinical application of WTD for neuropathic pain. A 579-gene consensus signature was identified that distinguished between sham and SNL samples, and a 456-gene consensus signature was identified that distinguished between WTD and SNL samples. Expression of 12 genes (Crk1, Fgf13, Fgfr1, Crk1, Adrbk1, Erbb3, Gnas, Vegfa, Crk1, Erbb3, Drd2, Gnas) were identified as the efficacy of differentially expressed genes.
Project description:As rats do not develop neuropathic pain like hypersensitivity as neonates post nerve injury but do as adults we have used these arrays to help define the processes involved in this process. Rat spinal cord (ipsilateral dorsal horn) was assayed 7 days post SNI injury to the sciatic nerve relative to sham injury. Two age groups of animals were tested Neonates (P10) and Adult (8-12wks). Experiment Overall Design: Six biologically indepenedent arrays were hybridized per assay point. Dorsal horn total RNA was prepared using standard Affymetrix protocols. Affymetrix Rat Expression 230A array used.