Collateral Sprouting of Peripheral Sensory Neurons Exhibits a Unique Transcriptomic Profile
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Collateral Sprouting of Peripheral Sensory Neurons Exhibits a Unique Transcriptomic Profile Dominique Lemaitre 1 & Maica Llavero Hurtado 2 & Cristian De Gregorio 3 & Maritza Oñate 4 & Gabriela Martínez 5,6,7 & Alejandra Catenaccio 8 & Thomas M. Wishart 2 & Felipe A. Court 7,8,9 Received: 18 March 2020 / Accepted: 8 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Peripheral 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. Keywords Axonal regeneration . Collateral sprouting . Nerve injury . Sciatic nerve . Transcriptome Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-01986-3) contains supplementary material, which is available to authorized users. * Felipe A. Court [email protected]
1
Facultad de Medicina, Centro de Fisiología Celular e Integrativa, Universidad del Desarrollo, Santiago, Chile
2
The Roslin Institute, University of Edinburgh, Edinburgh, UK
3
Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
4
Cristian De Gregorio [email protected]
Department of Physiology, Faculty of Biological Sciences, P
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