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Selected AbstractsNeural tube defects and impaired neural progenitor cell proliferation in G,1 -deficient miceDEVELOPMENTAL DYNAMICS, Issue 4 2010Hiroaki Okae Abstract Heterotrimeric G proteins are well known for their roles in signal transduction downstream of G protein,coupled receptors (GPCRs), and both G, subunits and tightly associated G,, subunits regulate downstream effector molecules. Compared to G, subunits, the physiological roles of individual G, and G, subunits are poorly understood. In this study, we generated mice deficient in the G,1 gene and found that G,1 is required for neural tube closure, neural progenitor cell proliferation, and neonatal development. About 40% G,1,/, embryos developed neural tube defects (NTDs) and abnormal actin organization was observed in the basal side of neuroepithelium. In addition, G,1,/, embryos without NTDs showed microencephaly and died within 2 days after birth. GPCR agonist-induced ERK phosphorylation, cell proliferation, and cell spreading, which were all found to be regulated by G,i and G,, signaling, were abnormal in G,1,/, neural progenitor cells. These data indicate that G,1 is required for normal embryonic neurogenesis. Developmental Dynamics 239:1089,1101, 2010. © 2010 Wiley-Liss, Inc. [source] Asymmetric localization of numb in the chick somite and the influence of myogenic signalsDEVELOPMENTAL DYNAMICS, Issue 3 2006Tamara Holowacz Abstract Whereas Notch signaling is known to play an essential role in the formation of somites, its role during later stages of somite maturation is less well understood. Here, we examine the signals and transcription factors that control the expression of the Notch antagonist, Numb, during somite maturation in the chick embryo. Numb mRNA is present in the epithelial somite and is increased in expression in the forming myotome. Numb protein displays a very specific subcellular localization and dynamic expression during somite maturation. Numb protein is asymmetrically localized in a cortical crescent on the basal side of dividing cells in the dorsomedial lip of the dermomyotome and is subsequently uniformly distributed throughout differentiated myotomal cells. Treatment of somites with either the combination of Wnt-3a and Shh, or ectodermal signals plus noggin, both of which induce somitic myogenesis, did not significantly affect Numb transcript levels but did lead to a dramatic increase in the levels of Numb protein, which was uniformly distributed throughout the cytoplasm of the resultant myotubes. Forced expression of MyoD in somites similarly induced high levels of Numb protein throughout the cytoplasm, without affecting Numb mRNA levels. We also found that signals that promote somitic myogenesis or forced MyoD expression induced expression of the Notch ligand, Serrate-2. Our findings suggest that Notch signals are specifically repressed in the myotome and that asymmetric expression of Numb in dividing cells of the dorsomedial lip of the dermomyotome may modulate whether these cells continue to divide or differentiate into myotomal cells. Developmental Dynamics 235:633,645, 2006. © 2006 Wiley-Liss, Inc. [source] Ultrastructure of an integumental organ with probable sensory function in Paragordius varius (nematomorpha)ACTA ZOOLOGICA, Issue 1 2004Andreas Schmidt-Rhaesa Abstract The cuticle of late parasitic stages of Paragordius varius (Leidy, 1851) is composed of a layer with large fibres and a second layer (often named the areolar layer) distal from it. In this paper, organs are described that start at the basal side of the epidermis, pass the epidermis and the fibrous layer of the cuticle and merge with large, cushion-like structures in the distal layer of the cuticle. The epidermal part of the organs is composed of darkly stained cells, which are probably in contact with the basi-epidermal nervous system. Up to four processes of this cell traverse the cuticle. These processes might include cilia, because they contain microtubule-like structures. The probable connection to nerve cells and the connection to the cushion-like structures in the outer cuticular layer make it likely that the organs described here are sensory in function. [source] Pax6 transcription factor is required for the interkinetic nuclear movement of neuroepithelial cellsGENES TO CELLS, Issue 9 2007Hiroshi Tamai The mammalian cerebral cortex develops from proliferative neuroepithelial cells that exhibit a cell cycle-dependent nuclear movement (interkinetic nuclear migration; INM). Pax6 transcription factor plays pivotal roles in various aspects of corticogenesis. From live observation using cultured cortical slices from the Pax6 mutant rat, we identified the premature descent of S phase cells, the unsteady ascent or descent of G2 phase cells, and ectopic cell division within the basal side of the ventricular zone (VZ). The centrosome normally stayed at the most apical side, apart from the nucleus, in the neuroepithelial cell during the S to G2 phase, while the Pax6 mutant showed unstable movement of the centrosome associated with an abnormal INM. Our results suggest the possibility that Pax6 regulates the INM by stabilizing the centrosome at the apical side. [source] Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines,HEPATOLOGY, Issue 4 2008Arnhild Schrage Transmigration through the liver endothelium is a prerequisite for the homeostatic balance of intrahepatic T cells and a key regulator of inflammatory processes within the liver. Extravasation into the liver parenchyma is regulated by the distinct expression patterns of adhesion molecules and chemokines and their receptors on the lymphocyte and endothelial cell surface. In the present study, we investigated whether liver sinusoidal endothelial cells (LSEC) inhibit or support the chemokine-driven transmigration and differentially influence the transmigration of pro-inflammatory or anti-inflammatory CD4+ T cells, indicating a mechanism of hepatic immunoregulation. Finally, the results shed light on the molecular mechanisms by which LSEC modulate chemokine-dependent transmigration. LSEC significantly enhanced the chemotactic effect of CXC-motif chemokine ligand 12 (CXCL12) and CXCL9, but not of CXCL16 or CCL20, on naive and memory CD4+ T cells of a T helper 1, T helper 2, or interleukin-10,producing phenotype. In contrast, brain and lymphatic endothelioma cells and ex vivo isolated lung endothelia inhibited chemokine-driven transmigration. As for the molecular mechanisms, chemokine-induced activation of LSEC was excluded by blockage of Gi -protein,coupled signaling and the use of knockout mice. After preincubation of CXCL12 to the basal side, LSEC took up CXCL12 and enhanced transmigration as efficiently as in the presence of the soluble chemokine. Blockage of transcytosis in LSEC significantly inhibited this effect, and this suggested that chemokines taken up from the basolateral side and presented on the luminal side of endothelial cells trigger T cell transmigration. Conclusion: Our findings demonstrate a unique capacity of LSEC to present chemokines to circulating lymphocytes and highlight the importance of endothelial cells for the in vivo effects of chemokines. Chemokine presentation by LSEC could provide a future therapeutic target for inhibiting lymphocyte immigration and suppressing hepatic inflammation. (HEPATOLOGY 2008.) [source] |