Thus, the Gas1 mutant displays similar enteric neural defects to that described for the Shh mutant.
It is imaginable that innate defects of the enteric glia network lead to a leaky mucosal barrier, which influences the adaptive immune system [ 6, 19].
Thus, there might be no relevant defects in the enteric glia network of UC patients, which is underlined by our results with a high secretion of GDNF during gut inflammation.
Additionally, our study reinforces data suggesting that enteric glia lesions and/or functional defects could be involved in the development of pathologies with altered barrier (such as inflammatory bowel diseases or colorectal cancer) and also be associated with increased barrier susceptibility to pathogen aggression.
Mice carrying the Ret.k- mutation were previously characterized and analysis of homozygous embryos has demonstrated that the aganglionic phenotype is due to an early defect of the enteric NC [30].
Using this system, they were able to detect very subtle structural ENS defects and demonstrated that enteric neurons require the planar cell polarity signaling components Celsr3 and Fzd3 for proper wiring.
Because Gas1 was suggested to inhibit Ret signaling by in vitro cell line assays (Cabrera et al., 2006; López-Ramírez et al., 2008), we wanted to determine whether the defect observed in Gas1 mutant enteric system is associated with elevated Ret signaling.
Because these defects usually occur in the absence of enteric pathogens, the term HIV enteropathy has been used [60], [62], [63].
HREM imaging proved inappropriate for detecting abnormalities in germ cells or the enteric nervous system; however, it was able to detect many additional defects, which were unreported in the earlier study.
Analysis of zebrafish mutants with altered epithelial survival reveals that seemingly related single gene defects have different effects on epithelial differentiation and smooth muscle and enteric nervous system development.
