Review Article Open Access
Volume 3 | Issue 1 | DOI: https://doi.org/10.33696/Signaling.3.064

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

  • 1University of Antwerp, Faculty of Medicine and Health Sciences, Department Antwerp Surgical Training, Anatomy and Research Center, Laboratory of Human Anatomy and Embryology, Universiteitsplein 1, 2610 Wilrijk (Antwerpen), Belgium
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Corresponding Author

Luc van Nassauw, vannassauw@uantwerpen.be

Received Date: September 10, 2021

Accepted Date: January 12, 2022


The enteric nervous system is the largest component of the autonomic nervous system. It contains a broad network of interconnected plexuses and enteric neuronal subtypes which are in charge of the normal functioning of the gastrointestinal tract. Vagal and sacral neural crest cells are at the basis of the enteric nervous system development. These cells undergo multiple processes such as migration, proliferation and differentiation to finally form a functional enteric nervous system. These processes are the result of multiple transcription factors, signaling molecules and pathways and their interactions, which all play essential roles in the enteric nervous system development. Malfunctioning or failing of one of these processes leads to congenital enteric neuropathies such as Hirschsprung’s disease, characterized by partial aganglionosis of the gastrointestinal tract. Since the current therapy brings many post-operative complications and a reduced quality of life, there is a high demand for alternative therapies such as stem cell therapy. To apply stem cell therapy, it is necessary that the factors involved in the differentiation process are known and thus that the process is fully understood. While migration and proliferation processes are largely unraveled, the differentiation process and its factors still remain largely unknown. This review describes the factors which have been identified so far and are involved in the differentiation and subtype specification of enteric neurons.


Enteric nervous system, Developmental biology, Transcription factors, Signaling molecules, Signaling pathways, Enteric neuron differentiation, Enteric neuron subtype specification

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