Background: Development of the enteric nervous system (ENS) requires interactions between migrating neural crest cells and the nascent gastrointestinal tract that are dependent upon genes expressed by both cell compartments. Hlx, a homeobox transcription factor gene that is expressed in mouse intestinal and hepatic mesenchyme, is required for normal embryonic growth of intestine and liver, and the Hlx^-/- genotype is embryonic lethal. We hypothesized that Hlx is required for ENS development. Results: Enteric neurons were identified in Hlx^+/+ and Hlx^-/- mouse embryos by immunostaining of embryo sections for the neural markers PGP9.5 and Phox2b, or by staining for β-galactosidase in whole-mount embryos containing the dopamine β-hydroxylase-nLacZ transgene. In Hlx^+/+ embryos, neural crest cells/enteric neurons have moved from the stomach into the intestine by E10.5. By contrast, neural crest cells/enteric neurons remain largely restricted to the lateral stomach mesenchyme of Hlx^-/- embryos, with only a few scattered neural crest cells/enteric neurons in the intestine between E10.5–16.5. Conclusion: The Hlx homeobox transcription factor is required for early aspects of ENS development.

Kaul A, et al. Pediatr Gastroenterol Hepatol Nutr. 2015 Dec;18(4):224-229. http://dx.doi.org/10.5223/pghn.2015.18.4.224