[Increased expression of HOXA9 gene in Hirschsprung disease].
OBJECTIVE
Hirschsprung disease is characterized by segmental aganglionosis of the terminal bowel. Neurons of the enteric nervous system arise from neural crest, migrate and colonize intestinal muscle coat where they proliferate and differentiate. The first pathophysiologic hypothesis suggests an absence of neural cell migration. The most recent hypothesis involves disorders of their homing and/or their differentiation due to an altered intestinal microenvironment.


METHODS
We analyzed the expression of muscle markers and laminin isoforms by immunocytochemistry and of homeotic genes involved in the regionalization of the intestinal mesenchyme during development (HOXA4, HOXA9, HOXD9) by RT-PCR, in colon specimens from two children with Hirschsprung disease (pathological and transition regions) and from healthy adult controls.


RESULTS
We showed an increase in HOXA9 gene expression in Hirschsprung disease specimens while HOXA4 and HOXD9 mRNA expressions were unchanged. No significant differences in the muscle markers nor in the laminin isoforms were noted.


CONCLUSIONS
These data suggest that intrinsic dysregulation of the intestinal wall microenvironment could account for the pathophysiology of Hirschsprung disease.
Méchine-Neuville
Agnès
A
INSERM Unité 381, Ontogenèse et Pathologie du Système Digestif, 3, avenue Molière, 67200 Strasbourg, France.
Lefebvre
Olivier
O
Bellocq
Jean-Pierre
JP
Kedinger
Michèle
M
Simon-Assmann
Patricia
P
D000328:Adult; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics; D005784:Gene Amplification; D005786:Gene Expression Regulation; D006627:Hirschsprung Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C088822:HOXD9 protein, human; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; C097899:homeobox protein HOXA9; C073547:HOXA4 protein, human