Pharmacological inhibition of transforming growth factor β signaling decreases infection and prevents heart damage in acute Chagas' Disease. Losartan prevents acquired epilepsy via TGF-b signaling suppression. Macrophage-derived factors stimulate optic nerve regeneration. Characterization of GDF-10 expression patterns and null mice. Localized expression of BMP and GDF mRNA in the rodent brain. Stem cell antigen-1 enhances tumorigenicity by disruption of growth differentiation factor-10 (GDF10)-dependent TGF-beta signaling. Targeting the TGFβ signalling pathway in disease. Bone morphogenetic proteins: facts, challenges, and future perspectives. Comparative integromics on BMP/GDF family. Growth/differentiation factor-10: a new member of the transforming growth factor-beta superfamily related to bone morphogenetic protein-3. Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke. Targeting the neural extracellular matrix in neurological disorders. Soleman, S., Filippov, M.A., Dityatev, A.
Neuronal intrinsic mechanisms of axon regeneration. Structural and functional plasticity in the somatosensory cortex of chronic stroke patients. Schaechter, J.D., Moore, C.I., Connell, B.D., Rosen, B.R. Rewiring the brain: potential role of the premotor cortex in motor control, learning, and recovery of function following brain injury. Upper limb recovery after stroke is associated with ipsilesional primary motor cortical activity: a meta-analysis. A role for ephrin-A5 in axonal sprouting, recovery and activity-dependent plasticity after stroke. An age-related sprouting transcriptome provides molecular control of axonal sprouting after stroke. In vivo voltage-sensitive dye imaging in adult mice reveals that somatosensory maps lost to stroke are replaced over weeks by new structural and functional circuits with prolonged modes of activation within both the peri-infarct zone and distant sites. Extensive cortical rewiring after brain injury. Thus, GDF10 is a stroke-induced signal for axonal sprouting and functional recovery.ĭancause, N. Using unsupervised genome-wide association analysis of the GDF10 transcriptome, we found that it was not related to neurodevelopment, but may partially overlap with other CNS injury patterns. RNA sequencing from peri-infarct cortical neurons revealed that GDF10 downregulated PTEN, upregulated PI3 kinase signaling and induced specific axonal guidance molecules. Using pharmacogenetic gain- and loss-of-function studies, we found that GDF10 produced axonal sprouting and enhanced functional recovery after stroke knocking down GDF10 blocked axonal sprouting and reduced recovery. GDF10 promotes axonal outgrowth in vitro in mouse, rat and human neurons through TGFβRI and TGFβRII signaling. Growth and differentiation factor 10 (GDF10) is induced in peri-infarct neurons in mice, non-human primates and humans.
Axonal sprouting in cortex adjacent to the infarct is part of this recovery process, but the signal that initiates axonal sprouting is not known. Stroke produces a limited process of neural repair.
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