Expression And Distribution Of BMP-2, 4 In Enteric Nervous System

The enteric nervous system(ENS) is the max peripheral nervous system,its abnormality can induce many congenital disease, for example Hirschsprung's disease(HD) and Hirschsprung allied diseases(HAD).Some studies indicate that the abnormal ENS in anorectal malformation(ARM) decrease, which may be the cause of dysfunction of rectum and the cause of constipation. But which factor can influce the ENS development and formation, and the period neural crest cell to ganglion cell remains unknown. It's reported that many factors have participated in ENS develop. These include nuclear transcription factors (HOX and NKX factors).Recent researches indicate that BMP-2/4 have important roles in mesoderm induction, allelotaxy and central neural development, but few report about their functions in ENS formation. By observing the expression of BMP-2/4 in bowel of SD rats with different ages, the distal rectum in fetal rats with anorectal malformation, the ganglionic(NG)and aganglionic(AG)segments of Hirschsprung's disease(HD),we want to know the functions of BMP-2 and BMP-4 during the enteric nervous system development. Which would give the direction for later reaserch.Methods The SP immunohistochemical method was used in the experiment to detected the expression of BMP-2/4 in bowel of SD rats with different ages, the distal rectum of fetal rats with anorectal malformation, the ganglionic(NG)and aganglionic(AG)segments of Hirschsprung's disease(HD). All the pictures were analyzed by the image analysis system. Results1.Expression of BMP-2 and BMP-4 in guts of rats The positive expression of BMP-2 and BMP-4 were found in full-thickness of guts. The neural crest cells were absent in the embryonic day (E) 12.5 rat gut, positive expression of BMP-2 appeared in the neural crest cells of Auerbach plexus and Meissner plexus in E16, the expression of BMP-2 could be seen in Auerbach plexus. BMP-2 showed strong positive in both nerve plexus when E20, while the expression of BMP-4 in Meissner plexus seemed weaker. After birth(7d),BMP-2 and BMP-4 had srong location in both nerve plexus. But in the guts of adult rat(4m), both BMP-2 and BMP-4 had slight positive expression in Auerbach plexus, and even weaker in Meissner plexus.2.Expression of BMP-2 and BMP-4 in the distal rectum of rat fetuses with anorectal malformationThe distal rectum of rat fetuses with anorectal malformation didn't communicate with outside in light microscope, the extreme intumescentiaed, mucous membrane formed reductus. The positive expression of BMP-2 and BMP-4 were found in mucosa, mesenchyme and nerve plexus, obviously decrease were found in the nerve plexus of distal rectum. There have significant differentce between the malformations and normal rat rectum.(P<0.05).3. Expression and significance of BMP-2,4 in Hirschsprung's diseasePositive expression of BMP-2,4 were found in normal control group and expanding segment. The stain of anti-BMP-2,4 were all low in myenteric nerve plexuses of transitional segment and strictural segment (P﹤0.05).There were no obvious difference in muscular layers(P>0.05).There was positive correlation between BMP-2 and BMP-4(P<0.05).Conclusions BMP-2 and BMP-4 can be found in ENS. Their expression shows time-dependent changes.They catched to the peak point in embryonic period. The decrease in the guts of ARM and the aganglionnic bowl implies that they maybe participate in the formation and maturation of enteric nervous system.