THYROID HORMONE-INDUCED APOPTOSIS OF LARVAL CELLS AND DIFFERENTIATIONOF PEPSINOGEN-PRODUCING CELLS IN THE STOMACH OF XENOPUS-LAEVIS IN-VITRO

It is generally known that the anuran stomach begins to express pepsin ogens (Pg) during metamorphosis. To clarify the mechanisms of differen tiation of Pg-producing cells, we examined immunohistochemically the e pithelial transformation from larval to adult form in Xenopus laevis s tomach at the cellular level. At the beginning of metamorphic climax, concomitantly with the modification of the basement membrane, apoptoti c cells labelled by TUNEL suddenly increased in number in the entire e pithelium except for the primordia of adult epithelial cells in the ba sal region of larval glands. Subsequently, with the development of con nective tissue, the adult epithelial cells actively proliferated and r eplaced the larval cells from the basal to the luminal region. Followi ng the start of morphogenesis of adult glands, Pg-producing cells beca me differentiated in newly formed adult glands, but not in the adult s urface epithelium. We then developed an organ culture system and exami ned effects of thyroid hormone (TH) on the differentiation of Pg-produ cing cells in X. laevis stomach in vitro. In the presence of TH, just as in spontaneous metamorphosis, Pg-producing cells differentiated fro m the adult epithelial primordia after the apoptosis of larval epithel ial cells. In contrast, in the absence of TH, neither apoptotic larval cells no Pg-producing cells were detected. There fore, we conclude th at TH triggers organ-autonomously the entire process leading to the di fferentiation of Pg-producing cells in X. laevis stomach. In addition, the strict localization of Pg-producing cells in the adult glands bot h in vivo and in vitro suggests the correlation between the differenti ation of Pg-producing cells and morphogenesis of the glands surrounded by the developed connective tissue.