Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

Neuropathological conditions might affect adult granulogenesis in the adult human dentate gyrus. However, radial glial cells (RGCs) have not been well characterized during human development and aging. We have previously described progenitor and neuronal layer establishment in the hippocampal pyramidal layer and dentate gyrus from embryonic life until mid-gestation. Here, we describe RGC subtypes in the hippocampus from 13 gestational weeks (GW) to mid-gestation and characterize their evolution and the dynamics of neurogenesis from mid-gestation to adulthood in normal and Alzheimer's disease (AD) subjects. In the pyramidal ventricular zone (VZ), RGC density declined with neurogenesis from mid-gestation until the perinatal period. In the dentate area, morphologic and antigenic differences among RGCs were observed from early ages of development to adulthood. Density and proliferative capacity of dentate RGCs as well as neurogenesis were strongly reduced during childhood until 5 years, few DCX+ cells are seen in adults. The dentate gyrus of both control and AD individuals showed Nestin+ and/or GFAPδ+ cells displaying different morphologies. In conclusion, pools of morphologically, antigenically, and topographically diverse neural progenitor cells are present in the human hippocampus from early developmental stages until adulthood, including in AD patients, while their neurogenic potential seems negligible in the adult.

Integrins play a pivotal role in organogenesis, by mediating the interactions between differentiating cells and the extracellular matrix. We analyzed the expression of integrins and their ligands during human liver organogenesis. The expression of ␤1, ␤3, and ␤4 integrins and the distribution of several extracellular matrix proteins were studied by immunoperoxidase in fetal liver samples from 5 to 40 weeks' gestation. Hepatoblasts expressed only the ␤1, ␣1, ␣5, ␣6, and ␣9 integrin chains. Fetal hepatocytes, emerging at the 8th week of gestation, initially retained the same combination of integrins, but presented a progressive decrease in their expression levels. After 15 weeks' gestation, the expression levels of ␤1, ␣1, ␣5, and ␣9 reached levels comparable to those observed in the adult state. ␣6 expression became undetectable after 30 weeks' gestation. As compared to hepatoblasts, intrahepatic biliary epithelial cells, differentiating at the 8th week of gestation in the ductal plate, were characterized by the progressive loss of ␣1, the marked induction of ␣6, and the de novo acquisition of the ␤4, ␣2, and ␣3 integrin chains. The disappearance of integrin receptors for laminin on hepatocytes was associated with the rarefaction of laminin in the perisinusoidal matrix, whereas their induction on biliary epithelial cells was associated with laminin deposition at the point of contact with the ductal plate. In conclusion, integrins likely play an important role in the differentiation of the epithelial and endothelial cell populations of the liver. (HEPATOLOGY 1998;26:839-847.)Integrins are membrane receptors for extracellular matrix proteins, which play an essential role in mediating the structural and functional interactions between cells and the extracellular matrix. 1 Previous studies have shown that markedly different combinations of integrins are expressed by the two populations of epithelial cells present in the adult liver, hepatocytes and biliary epithelial cells. [2][3][4] Like other simple epithelial cells, intrahepatic biliary epithelial cells express a large combination of integrin receptors, including the ␣2␤1, ␣3␤1, ␣5␤1, ␣6␤1, ␣9␤1, ␣V␤1, and ␣6␤4 dimers. 2,5 In striking contrast, the integrin repertoire of hepatocytes is restricted to the ␣1␤1, ␣5␤1, and ␣9␤1 dimers. This combination is highly distinctive. 3 The expression of ␣1␤1 integrin, a receptor for collagens and laminin, 6 is very unusual for an epithelial cell, since this integrin receptor is characteristically expressed by fibroblasts, muscle cells, and endothelial cells. Moreover, the absence of ␣6␤4, a characteristic component of hemidesmosomes, 7,8 is unique among the epithelial cells tested so far.It is likely that the differences in the combinations of integrins expressed, respectively, by hepatocytes and biliary epithelial cells are related to the differences in the constitution of their pericellular environments. Like all other lining epithelial cells, intrahepatic biliary epithelial cells are surrounded by a typical basement membran...