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The sympathetic nervous system in development and disease

Abstract

The sympathetic nervous system prepares the body for ‘fight or flight’ responses and maintains homeostasis during daily activities such as exercise, eating a meal or regulation of body temperature. Sympathetic regulation of bodily functions requires the establishment and refinement of anatomically and functionally precise connections between postganglionic sympathetic neurons and peripheral organs distributed widely throughout the body. Mechanistic studies of key events in the formation of postganglionic sympathetic neurons during embryonic and early postnatal life, including axon growth, target innervation, neuron survival, and dendrite growth and synapse formation, have advanced the understanding of how neuronal development is shaped by interactions with peripheral tissues and organs. Recent progress has also been made in identifying how the cellular and molecular diversity of sympathetic neurons is established to meet the functional demands of peripheral organs. In this Review, we summarize current knowledge of signalling pathways underlying the development of the sympathetic nervous system. These findings have implications for unravelling the contribution of sympathetic dysfunction stemming, in part, from developmental perturbations to the pathophysiology of peripheral neuropathies and cardiovascular and metabolic disorders.

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Fig. 1: Organization of the mouse sympathetic nervous system and timeline of developmental events.
Fig. 2: Axon growth and innervation of peripheral targets.
Fig. 3: Axonal trafficking of survival and apoptotic signals underlie a precarious balance between neuronal survival and death.
Fig. 4: Signalling mechanisms underlying dendrite growth and synaptogenesis in sympathetic ganglia.

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Acknowledgements

We thank Haiqing Zhao, Chris Deppmann, Raluca Pascalau and all members of the Kuruvilla laboratory for helpful comments. We apologize to authors whose work could not be cited due to space limitations. The authors’ work is supported by NIH R01 awards (NS114478 and NS107342) to R. Kuruvilla.

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Scott-Solomon, E., Boehm, E. & Kuruvilla, R. The sympathetic nervous system in development and disease. Nat Rev Neurosci 22, 685–702 (2021). https://doi.org/10.1038/s41583-021-00523-y

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