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PubMed1999

Transient upregulation of CBFA1 in response to bone morphogenetic protein-2 and transforming growth factor beta1 in C2C12 myogenic cells coincides with suppression of the myogenic phenotype but is not sufficient for osteoblast differentiation.

The bone morphogenetic protein (BMP)-2 is a potent osteoinductive signal, inducing bone formation in vivo and osteoblast differentiation from non-osseous cells in vitro. The runt domain-related protein Cbfa1/PEBP2alphaA/AML-3 is a critical component of bone formation in vivo and transcriptional regulator of osteoblast differentiation. To investigate the relationship between the extracellular BMP-2 signal, Cbfa1, and osteogenesis, we examined expression of Cbfa1 and osteoblastic genes during the BMP-2 induced osteogenic transdifferentiation of the myoblastic cell line C2C12. BMP-2 treatment completely blocked myotube formation and transiently induced expression of Cbfa1 and the bone-related homeodomain protein Msx-2 concomitant with loss of the myoblast phenotype. While induction of collagen type I and alkaline phosphatase (AP) expression coincided with Cbfa1 expression, Cbfa1 mRNA was strikingly downregulated at the onset of expression of osteopontin (OPN) and osteocalcin (OCN) genes, reflecting the mature osteoblast phenotype. TGF-beta1 treatment effectively suppressed myogenesis and induced Cbfa1 expression but was insufficient to support osteoblast differentiation reflected by the absence of ALP, OPN, and OCN. We addressed whether induction of Cbfa1 in response to BMP-2 results in the transcriptional activation of the OC promoter which contains three enhancer Cbfa1 elements. Transfection studies show BMP-2 suppresses OC promoter activity in C2C12, but not in osteoblastic ROS 17/2.8 cells. Maximal suppression of OC promoter activity in response to BMP-2 requires sequences in the proximal promoter (up to nt -365) and may occur independent of the three Cbfa sites. Taken together, our results demonstrate a dissociation of Cbfa1 expression from development of the osteoblast phenotype. Our findings suggest that Cbfal may function transiently to divert a committed myoblast to a potentially osteogenic cell. However, other factors induced by BMP-2 appear to be necessary for complete expression of the osteoblast phenotype.

Animals↗
PubMed1998

Commitment and differentiation of lung cell lineages.

To form a large diffusible interface capable of conducting respiratory gases to and from the circulation, the lung must undergo extensive cell proliferation, branching morphogenesis, and alveolar saccule formation, to generate sufficient surface area. In addition, the cells must differentiate into at least 40 distinct lung cell lineages. Specific transcriptional factors, peptide growth factor receptor-mediated signaling pathways, extracellular matrix components, and integrin-signaling pathways interact to direct lung morphogenesis and lung cell lineage differentiation. Branching mutants of the respiratory tracheae in Drosophila have identified several functionally conserved genes in the fibroblast growth factor signaling pathway that also regulate pulmonary organogenesis in mice and probably also in man. Key transcriptional factors including Nkx2.1, hepatocyte nuclear factor family forkhead homologues, GATA family zinc finger factors, pou and homeodomain proteins, as well as basic helix-loop-helix factors, serve as master genes to integrate the developmental genetic instruction of lung morphogenesis and cell lineage determination. Lung mesenchyme serves as a 'compleat' inducer of lung morphogenesis by secreting soluble peptide growth factors. In general, peptide growth factors signaling through cognate receptors with tyrosine kinase intracellular signaling domains such as epidermal growth factor receptor, fibroblast growth factor receptors, hepatocyte growth factor/scatter factor receptor, c-met, insulin-like growth factor receptor, and platelet-derived growth factor receptor, stimulate lung morphogenesis, while the cognate receptors with serine/threonine kinase intracellular signaling domains, such as the transforming growth factor-beta receptor family are inhibitory. The extracellular matrix also plays a key role in determining branching morphogenesis. Pulmonary neuroendocrine (PNE) cells differentiate earliest in gestation among lung epithelial cells. PNE cells are principally derived from endoderm and not neural crest. PNE cells have been proposed to function as airway chemoreceptors, while PNE cell secretory granules contain many bioactive substances such as GRP which may direct proliferation of adjacent epithelial cells. Mammalian achaete-schute homolog-1 null mutant mice do not develop PNE cells. Candidate molecular switches in the transition from a quiescent to a proliferative alveolar epithelial cell (AEC) phenotype and back again following acute hyperoxia, include autocrine peptide growth factor signaling pathways and cell cycle regulatory elements. AEC type 2 also appear capable of reversible transdifferentiation into AEC type 1 and intermediate phenotypes in response to cues from extracellular matrix and cell shape, as well as soluble factors. Evidence for expression of telomerase by alveolar epithelial stem cells, which correlates with self-renewal potential, is now beginning to emerge. Lung regeneration following lobectomy in juvenile rodents is associated with co-ordinated cell proliferation, re-expression of elastin and formation of alveoli. Retinoic acid has recently shown promise as a stimulator of alveolization in juvenile rats. Our future goal is to devise new rational and gene therapeutic strategies to stimulating lung growth and maturation, ameliorating lung injury, augmenting lung repair, and inducing lung regeneration. The ideal agent or agents would therefore mimic the instructive role of lung mesenchyme, correctly inducing the temporospatial pattern of lung cell lineages necessary to restore pulmonary gas diffusing capacity.

Animals↗
PubMed1999

In vitro pancreatic carcinogenesis.

Studies in our laboratories have indicated that pancreatic cancer originates not only from pancreatic ductal/ductular cells but also from within the Langerhans' islets, probably from reserve (precursor, stem) cells. To identify, enrich and characterize these cells, we established a long-term hamster islet culture and studied their growth, differentiation and response to the pancreatic carcinogen, N-nitrosobis(2-oxopropyl)amine (BOP). One group of cultured islets was treated in vitro with BOP (KL5B group) and the other group of islets served as an untreated control (KL5N group). During the early culture days, in both groups all cultured islets showed a progressive loss of endocrine cells and replacement by ductular, acinar and intermediary cells. However, all these cells disappeared after 35 days in culture and gave room to undifferentiated cells, which we believe represent stem cells. No differences were found between KL5N and KL5B cells with regard to cell growth and differentiation until day 35, when the growth of the KL5B cells accelerated and the cells underwent increasing pleomorphism and atypia. At day 133, KL5B cells but not KL5N cells showed colony formation in soft agar and formed invasive, poorly differentiated adenocarcinomas of the ductal type when transplanted into hamsters. All of these tumors showed mutation of the K-ras gene and extensive chromosomal damage. We concluded that like ductal/ductular cells, certain cell populations within islets are responsive to the carcinogenic effect of BOP. We could not ascertain whether these cells present a preexisting (stem, reserve) cell population within the islets or transdifferentiated islet cells.

Animals↗
PubMed1999

Kelletinin A, from the marine mollusc Buccinulum corneum, promotes differentiation in Hydra vulgaris.

The effects of kelletinin A [ribityl pentakis (p-hydroxybenzoate)] (KA), a natural compound isolated from the marine gastropod Buccinulum corneum, were studied in vivo in Hydra vulgaris during regeneration. KA caused a marked increase of regenerated tentacle numbers (ATN) and promoted transdifferentiation of epithelial cells into battery cells, and nematocyte differentiation. Morphological data were correlated to changes in acid and alkaline phosphatase levels, enzymes that have been described as regeneration markers.

Acid Phosphatase↗
PubMed2000

Is cadmium a cause of human pancreatic cancer?

Little is known about the etiology of pancreatic cancer, which is an important cause of cancer mortality in developed countries. We hypothesize that exposure to cadmium is a cause of pancreatic cancer. Cadmium is a nonessential metal that is known to accumulate in the human pancreas. The major risk factors for pancreatic cancer (increasing age, cigarette smoking, residence in Louisiana, and occupations involving exposure to metalworking and pesticides) are all associated with increased exposure to cadmium. Our meta-analysis of cohorts with high exposure to cadmium is also consistent with an increased risk of pancreatic cancer (standardized mortality ratio = 166; 95% confidence interval, 98-280; P = 0.059). Cadmium can cause the transdifferentiation of pancreatic cells, increases in the synthesis of pancreatic DNA, and increases in oncogene activation. Thus, cadmium is a plausible pancreatic carcinogen. The cadmium hypothesis provides a coherent explanation for much of the descriptive epidemiology of pancreatic cancer and suggests new avenues for analytical research.

Age Factors↗
PubMed2000

Alpha-smooth muscle actin expression in cultured lens epithelial cells.

PURPOSE: Lens epithelial cells transdifferentiate to myofibroblasts during the formation of anterior subcapsular cataracts and secondary cataracts. One of the defining characteristics of myofibroblasts is the expression of alpha-smooth muscle actin (alpha-SMA). This study investigated some of the factors that influence alpha-SMA expression in lens epithelial cells. METHODS: Bovine, rabbit, and human lens epithelial explants or cells were cultured with or without serum. Immunohistochemistry and immunoblotting were used to detect and quantitate alpha-SMA expression. RESULTS: Cells from all species studied expressed alpha-SMA in primary explant culture with or without serum. Immunostaining for alpha-SMA first appeared in a diffuse granular pattern, then accumulated at the cell cortex, and eventually was detected along stress fibers. When lens epithelial cells migrated onto cell-free regions of the capsule or were transferred to a plastic culture dish, alpha-SMA expression increased significantly. Expression of alpha-SMA positively correlated with cell size and cell migration. CONCLUSIONS: Expression of alpha-SMA is a common feature of cultured mammalian lens epithelial cells. Because alpha-SMA expression occurred without the addition of exogenous factors, the fibrosis seen in anterior subcapsular cataracts or secondary cataracts may reflect the intrinsic properties of lens epithelial cells. Interaction between lens epithelial cells and their substratum appears to be an important regulator of myofibroblast formation. Understanding the factors that regulate alpha-SMA expression in lens epithelial cells could lead to the development of methods for preventing secondary cataracts and anterior subcapsular cataracts.

Actins↗
PubMed2000

Overexpression of the transforming growth factor-beta-inducible gene betaig-h3 in anterior polar cataracts.

PURPOSE: In anterior polar cataracts and the fibrosis that can occur after cataract surgery, lens epithelial cells synthesize abundant extracellular matrix molecules and transdifferentiate into myofibroblast-like cells. Transforming growth factor (TGF)-beta has been implicated as a key player in these cataractous changes. The purpose of this study was to determine whether the TGF-beta-inducible gene h3 (betaig-h3) is expressed in lens epithelial cells from patients with anterior polar cataracts and to test whether betaig-h3 is induced by TGF-beta in cultured lens epithelial cells. METHODS: Lens epithelial cells attached to the anterior capsules of human cataractous lenses and noncataractous lenses were examined for the expression of betaig-h3 mRNA and protein using reverse transcription-polymerase chain reaction and immunohistochemical analyses. The effect of TGF-beta on betaig-h3 gene expression was also tested in human lens epithelial B-3 cells using Northern and Western blot analyses. RESULTS: betaig-h3 mRNA was not detected in lens epithelial cells from patients with clear lenses or patients with nuclear cataracts. Significant expression of mRNA for betaig-h3 was observed in lens epithelial cells from patients with anterior polar cataracts. Immunohistochemical analysis using anti-betaig-h3 antiserum indicated that betaig-h3 protein was present within the subcapsular plaques of anterior polar cataracts. Treatment of human lens epithelial B-3 cells with TGF-beta1 led to an increase in betaig-h3 mRNA and the secretion of betaig-h3 protein into the culture medium. CONCLUSIONS: betaig-h3 may serve as a marker for anterior polar cataracts in addition to previously known proteins, fibronectin, type I collagen, and alpha-smooth muscle actin. The functions of this protein in lens pathology need to be further investigated.

Animals↗
PubMed2000

[Morphogenesis and formation of a pattern in hydra. I. Distribution of morphogenetic potential].

True multicellularity is characterized by complex interactions between individual cells of the organism as well as by organization of cell masses into spatially and functionally determined structures promoting the exchange of information. Morphogenetic processes--genetically programmed generation of structures--always correlate with determination and maintenance of a pattern, i.e. a system of spatial relationships between them. Hydroid polyps provide a wide variety of approaches to study morphogenesis and patterning. Being comparatively simply organized, these animals have nevertheless certain developed mechanisms underlaying such processes as regeneration of missing structures, recovery of normal pattern after dissociation of polyps into single cells, tissue transdifferentiation in non-complementary chimaeras. An important feature of regeneration of hydroid polyps is its independence of the nerve net elements; the basis for regeneration is rather stored in epithelial cells and in their interactions. Phenomenological data, provided in the XVIII-XX centuries, allowed to propose several theoretical models of pattern regulation in hydra. The main goal of this paper is to review contemporary models of morphogenesis and patterning in the hydroid polyps.

Animals↗
PubMed2001

Bone morphogenetic protein-7 modulates genes that maintain the vascular smooth muscle cell phenotype in culture.

BACKGROUND: The vasculature is an important component in the musculoskeletal system, and vascularization is a key event in the development of normal cartilage and bone formation. Blood vessels deliver nutrients, oxygen, and precursor cells to maintain the structural and functional integrity of joints and soft and hard tissues. Therefore, agents that help to inhibit proliferation and retain the phenotype of vascular smooth muscle cells (SMCs) are of critical importance. In this study, we examined the capacity of bone morphogenetic protein-7 (BMP-7) to inhibit the proliferation of SMCs and maintain their phenotype. METHODS: A thymidine-incorporation assay was used to monitor the proliferative activity of SMCs on stimulation with platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta), agents known to be stimulatory for these cells. Reverse transcriptase-polymerase chain reaction (RT-PCR), Northern blot analysis, and enzyme-linked immunosorbent assay (ELISA) were used to monitor the modulation of various genes and gene products. Immunolocalization of SMC specific markers was also performed. RESULTS: BMP-7 inhibited both serum-stimulated and growth factor-induced (PDGF-BB and TGF-beta1) SMC growth, as measured by 3H-thymidine uptake and cell number, in primary human aortic smooth muscle (HASM) cell cultures. The addition of BMP-7 stimulated the expression of developmentally regulated as well as SMC-specific markers, namely, Id-1 and Id-2, alpha-actin, and SMC-specific heavy-chain myosin, as examined by semiquantitative and quantitative RT-PCR and by Northern blot analysis. Additionally, BMP-7 exhibited anti-inflammatory activity by downregulating intercellular adhesion molecule-1 (ICAM-1) expression. The collagen type III/I ratio that becomes lower with the transdifferentiation of SMCs into myofibroblasts is maintained in BMP-7-treated cultures compared with untreated controls. Studies on the mechanism of action indicate that BMP-7 treatment induces cyclin-dependent kinase-2 inhibitor, p21, which was inhibited during PDGF-BB-induced proliferation of SMCs. Finally, BMP-7 upregulates the expression of the inhibitory Smads, Smad6 and Smad7, which are known to inhibit TGF-beta superfamily signaling. CONCLUSIONS: These results suggest that BMP-7 maintains the expression of the vascular SMC phenotype. Thus, BMP-7 may prevent vascular proliferative disorders and potentially could act as a palliative agent following damage to the vasculature. CLINICAL RELEVANCE: In musculoskeletal disorders in which the vasculature plays an important role, BMP-7 may be of benefit as an anti-inflammatory and anti-proliferative agent for vascular endothelium and help maintain vascular integrity.

Animals↗
PubMed2001

Spemann's influence on Japanese developmental biology.

The discovery of the organizer by H. Spemann and Hilde Mangold, prompted a number of studies of embryonic induction in Japan. C.O. Whitman, N. Yatsu, T. Sato, H. Oka, T. Yamada, and Y.K. Okada were the pioneers in the field of embryonic induction. T. Yamada postulated the double potential theory for embryonic induction. O. Nakamura has modified the fate map of Vogt using newt and Xenopusblastulae. T.S. Okada and G. Eguchi proposed the new concept of "transdifferentiation" based on in vitro experiments in the retina and lens. T.S. Okada is not only an excellent scientist, but he has also nurtured many active developmental biologists. M. Takeichi, from his school, discovered the cell adhesion molecle, cadherin. Nakamura and colleagues tried to determine the origin and formation of the organizer. They performed recombination experiments using the ectoderm, endoderm and mesoderm, and concluded that the phenomenon in which various mesoderm tissues are formed by the recombination of the presumptive ectoderm with endoderm was "regulation of the vegetal-animal gradient". Some groups have also tried to purify specific inducing factors. T. Yamada and colleagues isolated two different types of ribonucleoproteins. I. Kawakami and colleagues showed that the ribosome fraction has neural inducing capacity, and that the extracellular matrix contains mesodermal inducing factors. Finally Asashima and colleagues isolated and identified activin A as a MIF factor. This finding had a great influence not only in the field of developmental biology, but also in molecular biology. Using activin, Asashima's group has successfully generated various organs, tissues, trunk-tail and head structures in vitro using animal caps (undifferentiated cells). Some other important molecules such as BMP, chordin and bFGF are also being studied by young Japanese scientists.

Amphibians↗
PubMed2000

[Regenerative potential in the organ of Corti after otic intoxication].

The auditory sensory cells are sensitive to a variety of influences such as noise, ototoxic drugs and aging. In the cochlea of mammals, the destroyed sensory cells are not replaced by new sensory cells. That leads to cochlear deafness, a frequent disease in human. Unfortunately, such auditory impairment is out of reach of treatment. The development of new therapeutic strategies in this field requires a precise knowledge of the mechanisms involved in auditory sensory cells disappearance and in organ of Corti's degeneration. The aim of our study was to characterize cellular and molecular changes in the cochlea of rats which had been intoxicated with the ototoxic antibiotic amikacin. The animals were sacrificed at different survival times during and after the antibiotic treatment and their cochleas were investigated using transmission and scanning electron microscopy and using confocal microscopy after tissue labellings with different fluorescent probes. The results revealed the existence of three periods. The first one corresponds to the disappearance of the sensory cells which die by apoptosis. During the second period, the organ of Corti undergoes a scarring process; concomitantly, a contingent of nonsensory supporting cells attempts to transdifferentiate directly into sensory cells. This process however fails, and the supporting cells never reach the status of hair cells. A general process of dedifferentiation of all the epithelial cells of the organ of Corti followed by a massive apoptosis of numerous epithelial cells and of most ganglion cells occurs during the third period. After that, the organ of Corti is definitely reduced to a simple monolayered epithelium. On the basis of these data, experimental strategies aimed i) to protect the sensory cells against apoptosis and ii) to promote sensory cell regeneration are now under study. They might have important implications in human therapy.

Amikacin↗
PubMed2000

[Human pancreatic stem cell and diabetes cell therapy].

Cell therapy offers today important perspectives for the treatment of type 1 diabetes. The current utilization of primary human islets of Langerhans nevertheless forbids all hope of developing this treatment on a large scale. The recent description of the persistence of stem cells capable of proliferating and differentiating in the adult pancreas offers an attractive alternative for the production in vitro of homologous insulin-secreting cells. We first reproduced in vitro from human islet preparations the proliferation of ductal epithelial structures and their progressive organization. Thereafter, we focused on the description of a reproducible source of human ductal cells by the transdifferentiation of exocrine preparations. More recently we described in these exocrine derived ductal cells the the expression the of insulin promoter factor-1 (IPF-1/otherwise known as PDX-1), a transcription factor essential for the differentiation of ductal cells into endocrine cells during both development and pancreatic regeneration. If the proliferation and differentiation of these cells is confirmed, this approach could lead to the description of an abundant source of human pancreatic stem cells for the production ex vivo of human insulin secreting cells and may even allow autologous cell therapy, in the absence of immunosuppression.

Cell Culture Techniques↗
PubMedDate not supplied

Trichostatin A, lead compound for development of antifibrogenic drugs.

Eukaryotic gene expression has mainly been studied in the context of trans-acting transcription factors and their interaction with regulatory cis-elements. Evidence is accumulating, that the higher order structure of chromatin also plays an essential role in eukaryotic gene expression. Hepatic stellate cells are the major cellular source of extracellular matrix synthesis in chronic liver diseases leading to fibrosis. We explored the antifibrogenic effect of the histone deacetylase inhibitor trichostatin A (TSA) on hepatic stellate cells in vitro. Primary hepatic stellate cells as well as activated, subcultured stellate cells were exposed to 10(-7) M-10(-9) M TSA. Collagens type I and III, and smooth muscle alpha-actin (alpha-SMA), a marker for transdifferentiation, were investigated at the protein and mRNA level by performing Northern hybridisation and quantitative immunoprecipitation. The antiproliferative effect was examined by 3H-thymidine incorporation and cell counting. Hyperacetylation of histone H4 was demonstrated by acid urea Triton-X-100 (AUT) polyacrylamide gel electrophoresis. TSA at 10(-7) M retarded the morphological changes characteristics for activation of primary stellate cells. Synthesis of collagens type I and III, and alpha-SMA was strongly inhibited at both protein and mRNA level. The proliferation rate of primary hepatic stellate cells was strongly suppressed by 10(-7) M TSA. Hyperacetylation of histone H4 showed to be maximal at 10(-7) M TSA. Primary hepatic stellate cells were more affected by TSA than subcultured stellate cells.

Animals↗
PubMed2002

Differential effect of activin A and BMP-7 on myofibroblast differentiation and the role of the Smad signaling pathway.

PURPOSE: To investigate myofibroblast differentiation and signal transduction induced by TGF-beta family members activin A and bone morphogenetic protein (BMP)-7. METHODS: Transcription of activin and receptors (ActR) for activin A and BMP-7 was detected by RT-PCR. Levels of marker proteins for differentiation and phosphorylation of similar to mothers against decapentaplegics (Smads) were quantified by Western blot analysis in response to BMP-7, activin A and follistatin. Transfection with antisense Smad2/3 was performed to evaluate signal transduction. RESULTS: Activin A and receptors (ActR-I, ActR-IB, ActR-II) are transcribed in corneal fibroblasts. Compared with TGF-beta1 or serum, activin A but not BMP-7 increased alpha-smooth muscle (SM) actin and actin-binding proteins such as SM myosin, alpha-actinin, and vinculin. Talin, paxillin, and desmin were not induced and vimentin was downregulated by activin. Activin also induced extracellular matrix proteins fibronectin and integrin beta1. Activin-dependent accumulation of proteins was blocked by follistatin. Regarding signal transduction, activin A induced phosphorylation of Smad 2, and BMP-7 induced Smad 1, both of which were inhibited by follistatin. Transfection with antisense Smad 2/3 prevented activin-induced expression and accumulation of alpha-SM actin. CONCLUSIONS: TGF-beta proteins have different functions in the cornea. Activin A and TGF-beta1, but not BMP-7, are regulators of corneal keratocyte differentiation and may play a role during myofibroblast transdifferentiation. Smad 2/3 signal transduction seems to be important in the regulation of muscle-specific genes. Further investigation of Smad signaling may help to better understand the function of TGF-beta family members in the cornea.

Activins↗
PubMed2000

An immunocytochemical profile of the endocrine pancreas using an occlusive duct ligation model.

CONTEXT: Ligation of the pancreatic duct, distally to its confluence into the bile duct has been shown to induce endocrine tissue regeneration. The surplus endocrine tissue formed is presumed to be able to replace pathologically and/or experimentally compromised tissue. OBJECTIVE: This is a quantitative study on the histology of duct ligated pancreas employing immunocytochemistry and computerised morphometry. INTERVENTIONS: Pancreatic duct ligation was performed on 25 groups of six normal Sprague-Dawley rats. Experimental animals were sacrificed at 12-hour intervals from day one to ten post-duct ligation and every 24 hours thereafter to day 14, the pancreas removed, fixed and processed. Six consecutive 3-6 micron serial sections were cut on a rotary hand microtome, floated onto 3-aminopropyl-trimethoxysilan coated slides and alternatively immunocytochemically stained for insulin, glucagon, pancreatic polypeptide and somatostatin. RESULTS: Pancreas transformation between days 1/2 and 3 1/2 was characterised by acinar deletion and the appearance of immunoreactive cells for the primary endocrine hormones. Transdifferentiation of existing endocrine tissue saw islet insulin core cells replaced by pancreatic polypeptide- and somatostatin positive cells, glucagon deletion and random appearance of all endocrine cell types within the inter-islet interstitium by day 3 1/2. Days 4 to 14 were characterised by cellular migration and islet reconstruction. CONCLUSIONS: To date our laboratory has investigated transplantation of foetal tissue beneath the renal capsule in syngeneic, isogeneic and allogeneic normal and diabetic rats. As pancreatic duct ligation induces the development of surplus endocrine tissue our next step would be to investigate the use of ligated pancreas as a replacement for foetal tissue.

Animals↗
PubMed2002

Cnidarians as a model system for understanding evolution and regeneration.

Hydra and Podocolyne are two cnidarian animals which provide complementary advantages for analysing developmental mechanisms possibly reflecting the basic developmental processes shared by most bilaterians. Interestingly, these mechanisms remain accessible all along the life of these animals, which bud and regenerate, whatever their age. The Hydra polyp permits a direct study of the molecular cascades linking amputation to regeneration. Podocoryne displays a complete life cycle, polyp and medusa stages with a fast and inducible sexual cycle and an unparalleled In vitro transdifferentiation potential. In both cases, a large number of evolutionarily conserved molecular markers are available, and analysis of their regulation highlights the molecular mechanisms which underly pattern formation in these two species.

Animals↗
PubMed2002

[Plasticity of tissue stem cells].

In the early stages of embryonic development, cells have the capability of dividing indefinitely and then differentiating into any type of cell in the body. Recent studies have revealed that much of this remarkable developmental potential of stem cells is retained by small populations of cells within most tissues in the adult. Intercellular signals that control the proliferation, differentiation and survival of tissue stem cells in their niches are being identified and include a diverse array of morphogens, cytokines, chemokines and cell adhesion molecules. Adult tissue stem cells, moreover, can also differentiate into developmentally unrelated cell types, such as nerve stem cells into blood cells. Currently, we can only speculate about the mechanisms involved in such dramatic changes in cell fate. For example, the emergence of, say, hematopoietic stem cells from brain neurospheres could involve either transdifferentiation (brain-->blood) or dedifferentiation (brain-->pluripotent cells), or by the actions of rare, but residual pluripotent stem cells. This issue is central to understanding the molecular basis of commitment and lies at the heart of debates about plasticity and the reversibility of developmental restriction.

Animals↗
PubMed2002

Lens epithelial cell death and reduction of anti-apoptotic protein Bcl-2 in human anterior polar cataracts.

PURPOSE: In light of the growing body of data implicating apoptosis in cataractogenesis, and in particular, the reported detection of apoptosis in posterior capsular opacification, the purported etiology of which, like that of anterior polar cataracts, is an aberrant transdifferentiation of lens epithelial cells into myofibroblastic cells, we hypothesized that apoptosis could also occur in anterior polar cataracts. Here we sought to examine whether apoptotic cell death occurs in lens epithelial cells from patients with anterior polar cataracts. METHODS: Cell death of lens epithelial cells from anterior polar cataracts, nuclear cataracts, and non-cataractous clear lenses was measured by TUNEL assay and DNA fragmentation assay. The expression of Bcl-2 and Bax was examined using reverse transcription-polymerase chain reaction and Western blot analysis. RESULTS: Cell death was detected in specimen from patients with anterior polar cataracts by TUNEL assay. DNA fragmentation assay showed the characteristic laddering pattern from the genomic DNA from anterior polar cataracts. The expression of Bcl-2 mRNA and its protein was markedly decreased in lens epithelial cells from patients with anterior polar cataracts. CONCLUSIONS: This study suggests that apoptotic cell death might occur in lens epithelial cells from anterior polar cataracts and decreased expression of Bcl-2 might play a role in the pathologic cellular mechanism of anterior polar cataracts.

Aged↗