BACKGROUND: Growth of the small intestine in the infant rat is promoted by crypt fission and later by increased crypt cell proliferation. Notch signaling could promote crypt fission. Hes-1 is a Notch target gene. AIM: We assessed the effect of Notch signaling on intestinal crypt fission and on growth of the intestine in the infant rat. METHODS: Hes-1 expression was determined in the small intestine of litters of Hooded Wistar rats aged between 3 and 72 days. Hes-1 RNA expression was measured by quantitative RT-PCR. Four groups of rats (n = 8 or 9) were injected daily, ip, either with vehicle or with the Notch inhibitor DAPT at doses of 3, 10, and 30 mg/kg, from days 9 to 13 of life, and killed on day 14. A microdissection technique was used to measure crypt fission, mitotic count, and apoptotic count. Data were analyzed by ANOVA and by use of Dunnett's F test. RESULTS: Hes-1 expression and crypt fission peaked on day 14. DAPT reduced Hes-1 immunostaining in proportion to dose. DAPT reduced villous area to 72 % (p < 0.01), 53 % (p < 0.001), and 38 % (p < 0.001) of control values for 3, 10 and 30 mg/kg doses, respectively, and reduced crypt fission to 53 % (p < 0.001) and 38 % (p < 0.001) of control values, respectively, for 10 and 30 mg/kg doses. Crypt mitotic count was not affected by any DAPT dose. DAPT at 10 and 30 mg/kg significantly increased apoptosis in crypts, by 6.5 and 4.8-fold, respectively. CONCLUSIONS: We conclude that Notch signaling promotes crypt fission and growth of the intestine by maintaining low apoptosis of crypt cells.
BACKGROUND: Growth of the small intestine in the infantrat is promoted by crypt fission and later by increased crypt cell proliferation. Notch signaling could promote crypt fission. Hes-1 is a Notch target gene. AIM: We assessed the effect of Notch signaling on intestinal crypt fission and on growth of the intestine in the infantrat. METHODS:Hes-1 expression was determined in the small intestine of litters of Hooded Wistar rats aged between 3 and 72 days. Hes-1 RNA expression was measured by quantitative RT-PCR. Four groups of rats (n = 8 or 9) were injected daily, ip, either with vehicle or with the Notch inhibitor DAPT at doses of 3, 10, and 30 mg/kg, from days 9 to 13 of life, and killed on day 14. A microdissection technique was used to measure crypt fission, mitotic count, and apoptotic count. Data were analyzed by ANOVA and by use of Dunnett's F test. RESULTS:Hes-1 expression and crypt fission peaked on day 14. DAPT reduced Hes-1 immunostaining in proportion to dose. DAPT reduced villous area to 72 % (p < 0.01), 53 % (p < 0.001), and 38 % (p < 0.001) of control values for 3, 10 and 30 mg/kg doses, respectively, and reduced crypt fission to 53 % (p < 0.001) and 38 % (p < 0.001) of control values, respectively, for 10 and 30 mg/kg doses. Crypt mitotic count was not affected by any DAPT dose. DAPT at 10 and 30 mg/kg significantly increased apoptosis in crypts, by 6.5 and 4.8-fold, respectively. CONCLUSIONS: We conclude that Notch signaling promotes crypt fission and growth of the intestine by maintaining low apoptosis of crypt cells.
Authors: Adrian G Cummins; Basile G Alexander; Adrian Chung; Edward Teo; Josh A Woenig; John B J Field; Fiona M Thompson; Ian C Roberts-Thomson Journal: Am J Gastroenterol Date: 2010-08-24 Impact factor: 10.864
Authors: Toshiro Sato; Johan H van Es; Hugo J Snippert; Daniel E Stange; Robert G Vries; Maaike van den Born; Nick Barker; Noah F Shroyer; Marc van de Wetering; Hans Clevers Journal: Nature Date: 2010-11-28 Impact factor: 49.962
Authors: Adrian G Cummins; Anthony G Catto-Smith; Donald J Cameron; Richard T Couper; Geoffrey P Davidson; Andrew S Day; Paul D Hammond; David J Moore; Fiona M Thompson Journal: J Pediatr Gastroenterol Nutr Date: 2008-08 Impact factor: 2.839