Notch signaling regulates cell differentiation and proliferation, contributing to the maintenance of diverse tissues including the intestinal epithelia. However, its role in tissue regeneration is less understood. Here, we show that Notch signaling is activated in a greater number of intestinal epithelial cells in the inflamed mucosa of colitis. Inhibition of Notch activation in vivo using a γ-secretase inhibitor resulted in a severe exacerbation of the colitis attributable to the loss of the regenerative response within the epithelial layer. Activation of Notch supported epithelial regeneration by suppressing goblet cell differentiation, but it also promoted cell proliferation, as shown in in vivo and in vitro studies. By utilizing tetracycline-dependent gene expression and microarray analysis, we identified a novel group of genes that are regulated downstream of Notch1 within intestinal epithelial cells, including PLA2G2A, an antimicrobial peptide secreted by Paneth cells. Finally, we show that these functions of activated Notch1 are present in the mucosa of ulcerative colitis, mediating cell proliferation, goblet cell depletion, and ectopic expression of PLA2G2A, thereby contributing to the regeneration of the damaged epithelia. This study showed the critical involvement of Notch signaling during intestinal tissue regeneration, regulating differentiation, proliferation, and antimicrobial response of the epithelial cells. Thus Notch signaling is a key intracellular molecular pathway for the proper reconstruction of the intestinal epithelia.

Msi-1 suppresses expression of Paneth cell-specific genes in IECs, presumably through a pathway independent from Notch or Wnt. These findings suggest Msi-1 is a negative regulator of Paneth cell differentiation, an may contribute to maintain the undifferentiated phenotype of ISCs.

ABSTRACT. The acoustic mode is the most reasonable means for social animals such as dolphins to maintain contact in the underwater habitat, and has been developed since they moved to the sea. This study investigates variations in dolphin vocalizations under the following conditions in a captive environment: 1) before feeding (Pre-feeding), 2) during feeding (Feeding), 3) during free time without the presence of people (Free), 4) during interaction with people located upon a float (Float), 5) during interaction with people in the water (Water). During the experiments, a total of 2642 whistles were extracted from sonogram data using a spectrogram. About 44% of the total whistles were observed during Pre-feeding (1171/2642), and the number recorded during Free, when people were absent, was the smallest. The acoustic contours of dolphin whistles differed in different situations: convex, wave, and trill whistles were made repeatedly during Pre-feeding, thereby being more common at this time than at other times. The situation of Feeding saw an increased number of Upsweeps, which might be related to the use of echolocation. The lower frequencies were recorded during Pre-feeding, reflecting the emotion related to the dolphin's hunger. The results of this study indicate that dolphins increase their vocalization during interaction with people, suggesting that interactions with dolphins provide an effective treatment for human health problems, which is discussed with a reference article in this study. Vocal data obtained during contact with humans might serve as an important index for the dolphinassisted therapy. KEY WORDS: bottlenose dolphin, captive environment, dolphin-human interaction, vocalization.J. Vet. Med. Sci. 69(2): 165-170 2007 Bottlenose dolphins, Tursiops truncatus, are kept in many aquaria and marine facilities throughout the world. They have a wide distribution and inhabit almost every ocean. The brain of the bottlenose dolphin is heavier than that of the human brain, and the bottlenose dolphin's brain index {brain weight/(body size) 2/3 }, which is the ratio of brain size to body size, is the second-largest (0.64) of all mammals after humans (0.89); this value is more than twice that of chimpanzees (0.30) [16]. Dolphins have developed a complex social structure [8] and make use of tools [13]. Several experiments that target cognitive mechanisms have demonstrated dolphins' capabilities in terms of learning, memory, and communicative language [11].Most marine-derived dolphins form communities, called pods, and are considered to mutually communicate. They often use characteristic vocalizations for communication rather than touch and breaching [24]. The dolphin has developed a means of sound communication that can carry a wide range and send myriad messages rapidly through water. Dolphins gather information through hearing. Their sophisticated communication system improves their efficiency in searching for food, reproduction, and protection; thereby enhancing their adaptation to the environment [6].Dolphin...

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