BACKGROUND: Hirschsprung disease (HSCR) is a congenital disorder characterized 
by an absence of intrinsic ganglion cells in the nerve plexuses of the lower 
colon. The Semaphorin 3A (SEMA3A) gene is involved in the migration of enteric 
neural precursors (ENPs). To analyze the function of SEMA3A in HSCR, the SEMA3A 
expression in different colon segments in HSCR was examined.
METHODS: The expression levels of SEMA3A in both ganglionic and aganglionic 
colon tissues of 32 patients with HSCR and in colon tissue of 5 newborn 
unaffected individuals were examined by real-time RT-PCR, Western-blot, and 
immunohistology.
RESULTS: Comparison of SEMA3A expression levels between ganglionic and 
aganglionic tissues in HSCR revealed upregulation of SEMA3A expression in 43.75% 
(14/32) of the aganglionic colons. SEMA3A was expressed in the ganglion cells of 
the myenteric plexus, submucosa, as well as in the longitudinal and circular 
muscle layer of the normal colon of both unaffected newborns and patients with 
HSCR. In the aganglionic segment of patients with HSCR, SEMA3A was highly 
expressed in the circular muscle layer and was also detected in the submucosa 
and in the longitudinal muscles layer. The fluorescence intensity of SEMA3A in 
the circular muscle layer in the aganglionic segment was much higher than that 
in ganglionic segment (p < .001).
CONCLUSION: SEMA3A expression was upregulated in the aganglionic smooth muscle 
layer of the colon in some patients with HSCR and our data suggest that 
increased SEMA3A expression may be a risk factor for HSCR pathology in a subset 
of patients.