Interplay among enteric neurons, interstitial cells of Cajal, resident and not resident connective tissue cells

is well known that gut motility is regulated by the neurons of the enteric nervous system (ENS), in particular by those located within the ganglia of the myenteric (Auerbach) plexus. John Furness et al. [1] have amply documented that the ENS is composed of a complex network of neurons and in the last decades, utilizing a variety of sophisticated immunohistochemical, electro-physiological, pharmacological and tracing techniques, a variety of subtypes of neurons have been identified differing from each other by a combination of morphology, neurotransmitters, elec-trophysiology, target tissue and direction and length of axon projection. Importantly, few decades ago it has been demonstrated unequivocally that gut motility is also regulated by the so-called interstitial cells of Cajal (ICC) [2, 3], which in turn are under enteric neuron control [3–5]. The target of both neurons and ICC are the smooth muscle cells (SMC). Briefly, two cell players are the leaders in gut motility, the neurons and the ICC, being the SMC executive cells only. The first review that will appear in this series is that of Eather Young, one of the most experts in ENS development. This review deals on the birthdating of the different neuron subtypes and the unexpected steps they follow to achieve their final specific chemical coding, underlying on the mechanisms controlling enteric neu-ron differentiation and development of enteric neuronal microcir-cuits in animals and human beings. Moreover, Eather Young stresses fascinating and not fully understood clues on the formation of the enteric neural circuits that is dependent on the generation of the specific neuronal subtypes, their specific projections and connections. Among these clues: why some neurotransmit-ters or their synthesizing enzymes, or combinations of neurotrans-mitters, which are not expressed in the mature nervous system, are expressed transiently in the developing ENS, and how neuron diversity is generated at the appropriate sites from apparently identical neural crest-derived cells. The latter is a central question in neurogastroenterology, as defects in this process are likely the cause of some paediatric motility disorders. There is some more evidence in recent years that a co-presence of ICC and neuron defects is often correlated with a clinical outcome poorer than that in the presence of an ICC or a neuronal defect alone. As an example, delay in neuronal development or neuron immaturity that directly cause dysmotility can negatively influence the ICC number or differentiation and, consequently, also ICC functioning. In a forthcoming review, all information on …