Differentiation and Subtype Specification of Enteric Neurons: Current Knowledge of Transcription Factors, Signaling Molecules and Signaling Pathways Involved

Abstract

The enteric nervous system (ENS) forms the largest component of the autonomic nervous system (ANS). In humans, it contains between 200 and 600 million neurons which are part of intrinsic neuronal circuits managing to generate reflex gastrointestinal (GI) contractile activity without intervention of the central nervous system (CNS) [1,2]. The ENS is located along the length of the GI tract and oversees controlling the main functions such as secretion, motility, and blood flow. In addition, it is also responsible for the communication with the immune system and microbiome [3–5]. The ENS contains a network of neurons and glial cells which are dispersed over two major ganglionated and interconnected plexuses, the myenteric (Auerbach) plexus, and the submucosal (Meissner) plexus. In larger mammals, the submucosal plexus is further subdivided into smaller plexuses [4,6-10]. The neurons of the myenteric plexus are primarily involved in GI motility regulation, while the neurons of the submucosal plexus are involved in the regulation of secretion and vascular tone [3,6,11,12]. The ENS is a highly complex nervous system of which the functioning is dependent on many different neuronal subtypes. To keep an overview of the neuronal subtypes, they are categorized in different classes according to certain characteristics. Among these features are their morphology, electrical properties, chemical coding, and Abstract