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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-n LacZ  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.

The Hlx homeobox transcription factor is required early in enteric nervous system development