Abstract

The post-ganglionic sympathetic neurons play an important role in modulating visceral functions and maintaining homeostasis through complex and reproducible axonal and dendritic connections between individual neurons and with their target tissues. Disruptions in these connections and in sympathetic nervous system function are observed in several neurological, cardiac and immune-related disorders, which underscores the need for understanding the mechanisms underlying neuronal polarity, axonal growth and dendritic growth in these neurons. The goals of this chapter are to explore our current understanding of the various growth factors, their signaling pathways, downstream effectors and interplay between these pathways to regulate different stages of axonal and dendritic growth in sympathetic neurons.

Highlights

  • The sympathetic nervous system is an important component of the peripheral autonomic nervous system responsible for controlling the visceral functions of the body to maintain homeostasis and the “flight or fight response” [1]

  • Early studies suggest a role for Artemin in sympathetic neuron survival with the superior cervical ganglia being smaller in Artemin, Ret and GFRα3 knockout animals compared to wild type animals [29, 32], more recent studies suggest that the decreased neuronal cell numbers in the absence of Artemin signaling are an indirect effect of aberrant axonal migration and target innervation [28]

  • In addition to nerve growth factor (NGF), neurotrophin-3 is expressed in sympathetic neurons, its main receptor TrkC is expressed at low levels in neonatal sympathetic neurons [44, 79–81]

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Summary

Introduction

The sympathetic nervous system is an important component of the peripheral autonomic nervous system responsible for controlling the visceral functions of the body to maintain homeostasis and the “flight or fight response” [1]. SCG neurons are one of the most studied to understand various aspects of neuronal development in the peripheral nervous system. Autonomic Nervous System as Parkinson’s disease, cardiac disorders, multiple system atrophy, multiple sclerosis, diabetes and immune-related disorders, has renewed an interest in understanding neuronal development and maintenance of sympathetic neurons [3–11]. The precursors of the post-ganglionic sympathetic neurons are derived from the trunk neural crest cells, which migrate ventrally along the neural tube, through the anterior portion of the sclerotome and coalesce near the dorsal aorta to form the sympathetic ganglia [12]. Studies on the early sympathetic neuron specification and neural crest migration show that growth factors such as neurotrophins, semaphorins and ephrins are important for migration of these neural crest cells, with bone morphogenetic proteins (BMPs) being important for their differentiation into sympathetic neuronal lineage. We will explore the pathways that are important for establishing and refining axonal and dendritic arbors in sympathetic neurons

Growth factors and signaling pathways involved in axonal growth
Hepatocyte growth factor
Artemin
Neurotrophins
Nerve growth factor
Neurotrophin 3 (NT-3)
Brain-derived neurotrophic factor (BDNF)
Tumor necrosis factor superfamily
Extracellular matrix proteins
Other signaling pathways involved in axonal growth
Growth factors and signaling pathways involved in dendritic growth regulation
Bone morphogenetic proteins (BMPs)
Neuronal activity dependent dendritic growth
Nerve growth factor and fibroblast growth factor
Cytokines
Cytoskeletal proteins
Other signaling pathways involved in dendritic growth
Findings
Limitations of current research and the path forward
Full Text
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