Anti-apoptotic role of Sonic hedgehog protein at the early stages of nervous system organogenesis

In vertebrates the neural tube, like most of the embryonic organs, shows discreet areas of programmed cell death at several stages during development. In the chick embryo, cell death is dramatically increased in the developing nervous system and other tissues when the midline cells, notochord and floor plate, are prevented from forming by excision of the axial-paraxial hinge (APH), i.e. caudal Hensen's node and rostral primitive streak, at the 6-somite stage ( Charrier, J. B., Teillet, M.-A., Lapointe, F. and Le Douarin, N. M. (1999). Development 126, 4771-4783). In this paper we demonstrate that one day after APH excision, when dramatic apoptosis is already present in the neural tube, the latter can be rescued from death by grafting a notochord or a floor plate fragment in its vicinity. The neural tube can also be recovered by transplanting it into a stage-matched chick embryo having one of these structures. In addition, cells engineered to produce Sonic hedgehog protein (SHH) can mimic the effect of the notochord and floor plate cells in in situ grafts and transplantation experiments. SHH can thus counteract a built-in cell death program and thereby contribute to organ morphogenesis, in particular in the central nervous system.     

The role of seed coat in early stages of soybean germination

The presence of the seed coat delays the early stages of germination of soybean embryos. This retardation seems to be due to the seed coat acting as a mechanical barrier to seedling. Although entire soybean seeds are insensitive to light, removal of the seed coat induces a light requiring condition. The early germination of naked seeds or isolated embryonic axes is enhanced by darkness. Red light produced a similar effect as white, providing evidence for the effective wavelength of the photo-inhibition. Far-red light acted similarly to darkness in promoting the early germination of the embryos. It is suggested that possibly light may act through phytochrome by the high irradiance system.     

Localization of HB9 homeobox gene mRNA and protein during the early stages of chick feather development

We performed in situ hybridization and immunohistochemical analysis of HB9 homeobox gene mRNA and protein, respectively, during chick feather development. HB9 mRNA was highly expressed in epidermal basal cells and dermal cells of the placodes and feather buds, but not in those of the interplacodes and interbud regions. HB9 protein was predominantly expressed in dermal cells of the symmetric short buds and decreased after the asymmetric bud stage when the feather bud had become elongated along the anterior-posterior (A-P) and proximal-distal (P-D) axis. These results suggest that HB9 gene is regulated in a spatiotemporal manner during feather development, and may be involved in early feather bud morphogenesis.     

The role of host-derived heat-shock protein in immunity against Toxoplasma gondii infection

Heat-shock proteins (HSPs) are evolutionarily highly conserved polypeptides synthesized by cells to preserve cellular functions under a variety of stressful conditions, including infections. In infections, both host cells and pathogens express HSPs, although the role of these molecules in the host-pathogen relationship is elusive. Here, Hajime Hisaeda and Kunisuke Himeno show that a correlation exists between the 65 kDa HSP molecule (HSP65) and protection against Toxoplasma gondii infection, suggesting that this protein contributes to the host defense system. These findings may help in the understanding of the complicated host-parasite relationship.     

The role of glycogen synthase kinase 3 in the early stages of Alzheimers' disease

There are two different types of Alzheimers’ disease, familiar Alzheimers’ disease (FAD) and Sporadic Alzheimers’ disease (SAD), and the origin of the disease could be different in both familial and sporadic cases. In terms of FAD, mutations in three different genes are likely to promote the onset of the disease whereas for SAD, different risk factors might be involved. Nevertheless, downstream of the initial causes of the disease some common factors may be involved. In this review, rather than the differences, we have focused on some of the common features shared by Alzheimers’ patients, irrespective of the origin of their disorder. Among these common features, at the molecular level, the activation of the protein kinase GSK3 may be relevant.     

The role of mRNA and protein stability in gene expression

How important is the stability of gene products in the process of gene expression? We use a dual-compartment mathematical model to demonstrate the effects that changing the rates of synthesis and degradation of hypothetical mRNAs and proteins would have on the final concentration of protein. The model predicts that the concentration of protein at steady state equals the product of the rate constants for synthesis of mRNA and protein (ks1 and ks2) divided by the product of the rate constants for degradation (kd1 and kd2) and that the rate at which protein concentration changes depends on the rate constants for degradation of both the mRNA and the protein. This permits great flexibility in controlling induction kinetics for particular gene products, since their synthesis, translation, and degradation may be regulated coordinately to permit induction to be stable or transient or to amplify the final yield of protein. We suggest single exons may encode structural features that cause both mRNAs and proteins to be labile, thereby ensuring that modal stabilities of highly regulated macromolecules are similar.     

The role of C3 as an opsonin in the early stages of infection.

In order to investigate the role of C3 in host defense in vivo, normal AKR/J mice, genetically deficient in C5, were depleted of serum C3 by the injection of purified cobra venom factor (CoVF). Concurrent with their C3 depletion, their serum opsonizing activity decreased to a level less than 20% of normal. When these mice were challenged with an intraperitoneal injection of pneumococci 2 hr after the CoVF treatment, the LD50 was from 30 to 80 times lower than the LD50 in saline-treated control animals. When the CoVF was given only 6 hr after the pneumococcal challenge, the LD50 was the same as in the control mice. If the pneumococci were first preopsonized in vitro and then injected into CoVF-treated animals, the LD50 was the same as that in control animals. These experiments demonstrate that C3 plays a significant role in vivo in the host's defense against infection and that a major part of that role is through its action as an opsonin. Furthermore, these experiments demonstrate that the role of C3 is most significant during the early stages of bacterial invasion.     

Genetic dissection of the early stages of protein secretion in yeast

The earliest events in the export of secretory proteins from eukaryotic cells are their insertion into and transport across the membrane of the endoplasmic reticulum, followed by signal peptide cleavage and transfer of core oligosaccharides to specific asparagine residues. Much has been learned through reconstitution of these processes in vitro using cell-free extracts prepared from mammalian and yeast cells. Now, a combination of genetic, molecular and biochemical approaches are being employed to study the early stages of protein secretion in the yeast Saccharomyces cerevisiae.     

Intermediate filament protein expression in early developmental stages of the mouse

Expression patterns of intermediate filament proteins have been studied during early mouse embryo development. For this purpose, pre-implantation embryos at different stages of development after in vitro fertilization were studied using antibodies to cytokeratins, vimentin and lamins, using the indirect immunofluorescence assay. The levels of expression were quantitated and localization of the protein constituents was assessed by means of confocal scanning laser microscopy. Our studies showed that, although the embryos grew in culture, vimentin could not be detected in a filamentous organization. Immunofluorescence for cytokeratins was only positive from the 8-cell stage onwards. In the morula stage an increased level of cytokeratin expression was observed with a transitional staining pattern, combining a filamentous and a diffuse occurrence. In the blastocyst stages profound cytokeratin filaments were seen in trophoblast cells but not in the inner cell mass. When the cytokeratin subtypes were analysed separately, it became apparent that expression levels of cytokeratins 8 and 18 increased gradually up to a filamentous pattern in the blastocyst stage. Cytokeratins 7 and 19, although elevated in the latter stage and showing a filamentous distribution, were not found as prominently as cytokeratins 8 and 18. A-type as well as B-type lamins could be detected in all developmental stages examined, as a faintly reactive nuclear lamina. In blastocysts both lamin types were detected in trophoblast as well as in inner cell mass.