Innervation in organogenesis

Abstract

Proper innervation of peripheral organs helps to maintain physiological homeostasis and elicit responses to external stimuli. Disruptions to normal function can result in pathophysiological consequences. The establishment of connections and communication between the central nervous system and the peripheral organs is accomplished through the peripheral nervous system. Neuronal connections with target tissues arise from ganglia partitioned throughout the body. Organ innervation is initiated during development with stimuli being conducted through several types of neurons including sympathetic, parasympathetic, and sensory. While the physiological modulation of mature organs by these nerves is largely understood, their role in mammalian development is only beginning to be uncovered. Interactions with cells in target tissues can affect the development and eventual function of several organs, highlighting their significance. This chapter will cover the origin of peripheral neurons, factors mediating organ innervation, and the composition and function of organ-specific nerves during development. This emerging field aims to identify the functional contribution of innervation to development which will inform future investigations of normal and abnormal mammalian organogenesis, as well as contribute to regenerative and organ replacement efforts where nerve-derived signals may have significant implications for the advancement of such studies.

Keywords: Development; Innervation; Neuron; Organogenesis; Parasympathetic; Sensory; Sympathetic.

Fig. 1

During development neural crest cells migrate to sites such as ganglia, where they differentiate into neurons of the peripheral nervous system. Neural crest cells can directly give rise to sensory, sympathetic, and enteric neurons or indirectly to parasympathetic neurons.

Fig. 2

Postganglionic neurons, such as those of the sympathetic nervous system, innervate target organs. Neurotrophins produced by the target tissue bind their specific neuronal receptors to promote growth and survival of the neuron. Additionally, guidance cues secreted by the target tissue interact with their respective neuronal receptors to guide axons within the tissue, inducing attractive or repulsive growth responses.

Fig. 3

Axon terminals form synapses with target cells during organogenesis. Neurotransmitters released from the neurons bind their respective receptors on the target cell to induce a cellular response. Examples of developmental processes modulated by these responses include the timing of cardiomyocyte cell cycle withdrawal, the regulation of pancreatic islet architecture, and modulation of salivary gland tubulogenesis.