Collateral Sprouting of Peripheral Sensory Neurons Exhibits a Unique Transcriptomic Profile

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dc.contributor.authorLemaitre, Dominique
dc.contributor.authorLlavero Hurtado, Maica
dc.contributor.authorGregorio, Cristian de
dc.contributor.authorOñate, Maritza
dc.contributor.authorMartínez, Gabriela
dc.contributor.authorCatenaccio, Alejandra
dc.contributor.authorWishart, Thomas M.
dc.contributor.authorCourt, Felipe A.
dc.date.accessioned2021-08-06T17:35:02Z
dc.date.available2021-08-06T17:35:02Z
dc.date.issued2020
dc.description.abstractPeripheral nerve injuries result in motor and sensory dysfunction which can be recovered by compensatory or regenerative processes. In situations where axonal regeneration of injured neurons is hampered, compensation by collateral sprouting from uninjured neurons contributes to target reinnervation and functional recovery. Interestingly, this process of collateral sprouting from uninjured neurons has been associated with the activation of growth-associated programs triggered by Wallerian degeneration. Nevertheless, the molecular alterations at the transcriptomic level associated with these compensatory growth mechanisms remain to be fully elucidated. We generated a surgical model of partial sciatic nerve injury in mice to mechanistically study degenerationinduced collateral sprouting from spared fibers in the peripheral nervous system. Using next-generation sequencing and Ingenuity Pathway Analysis, we described the sprouting-associated transcriptome of uninjured sensory neurons and compare it with the activated by regenerating neurons. In vitro approaches were used to functionally assess sprouting gene candidates in the mechanisms of axonal growth. Using a novel animal model, we provide the first description of the sprouting transcriptome observed in uninjured sensory neurons after nerve injury. This collateral sprouting-associated transcriptome differs from that seen in regenerating neurons, suggesting a molecular program distinct from axonal growth. We further demonstrate that genetic upregulation of novel sproutingassociated genes activates a specific growth program in vitro, leading to increased neuronal branching. These results contribute to our understanding of the molecular mechanisms associated with collateral sprouting in vivo. The data provided here will therefore be instrumental in developing therapeutic strategies aimed at promoting functional recovery after injury to the nervous system.es
dc.identifier.citationMolecular Neurobiology, 2020 vol. 57:4232–4249es
dc.identifier.urihttps://doi.org/10.1007/s12035-020-01986-3es
dc.identifier.urihttp://hdl.handle.net/11447/4253
dc.language.isoenes
dc.subjectAxonal regenerationes
dc.subjectCollateral sproutinges
dc.subjectNerve injuryes
dc.subjectSciatic nervees
dc.subjectTranscriptomees
dc.titleCollateral Sprouting of Peripheral Sensory Neurons Exhibits a Unique Transcriptomic Profilees
dc.typeArticlees

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