The Hlx homeobox transcription factor is required early in enteric nervous system development.
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 beta-galactosidase in whole-mount embryos containing the dopamine beta-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.


CONCLUSIONS
The Hlx homeobox transcription factor is required for early aspects of ENS development.
Bates
Michael D
MD
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. michael.bates@cchmc.org
Dunagan
Dana T
DT
Welch
Lynn C
LC
Kaul
Ajay
A
Harvey
Richard P
RP
D000818:Animals; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D017615:Enteric Nervous System / Q000196:embryology* / Q000378:metabolism; D005260:Female; D041981:Gastrointestinal Tract / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D007763:Lac Operon / Q000235:genetics; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
C489999:Hlx protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors; D004299:Dopamine beta-Hydroxylase; D001616:beta-Galactosidase