Mechanisms of respiratory innervation during embryonic development

Abstract

During embryogenesis, the development of the respiratory tract is closely associated with the formation of an extensive neuronal network. While the topic of respiratory innervation is not new, and similar articles were published previously, recent studies using animal models and genetic tools are breathing new life into the field. In this review, we focus on signaling mechanisms that underlie innervation of the embryonic respiratory tract.

Keywords: brain-derived neurotrophic factor; extrinsic neuron; glial cell-derived neurotrophic factor; intrinsic neuron; lung development; neurotrophin; respiratory tract.

Figure 1. Schematic diagram showing extrinsic nerves and intrinsic innervation of the respiratory tract. (A) Extrinsic neurons have their cell bodies in the jugular, nodose, and petrosal ganglia within the brainstem. These extrinsic neurons extend their axons via the vagus nerve (in red and blue) and provide sensory and parasympathetic respiratory innervation respectively. In addition, sensory neurons located in the dorsal root ganglion also provide extrinsic innervation (in green) to the respiratory tract. (B) Neural crest-derived intrinsic neurons (in blue) cluster within the trachea and main bronchi. Intrinsic neurons express the Ret receptor. The survival, proliferation, and/or differentiation of intrinsic neurons within the respiratory tract is dependent on the GDNF family ligands that include GDNF and neurturin. (C) ASM in the embryonic lung expresses BDNF. BDNF serves as a target-derived neurotrophic signal for extrinsic innervation by TrkB⁺ extrinsic nerves. The lung is largely devoid of intrinsic neurons.