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Cell Differentiation (cell + differentiation)
Kinds of Cell Differentiation Terms modified by Cell Differentiation Selected AbstractsDendritic Cell Differentiation and Maturation in Embryonic Rat Liver: Immunohistochemistry and Electron Microscopy with Reference to Dendritic Cell ContactsANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2 2005N. El-Nefiawy Summary This study investigated the dendritic cell (DC) differentiation in embryonic rat liver utilizing in situ ultrastructural characterization and immunohistochemistry. The study revealed the existence of DCs early in hepatic ontogeny with positive immune staining to the OX-62 monoclonal antibody. DCs existed in three differentiating stages: immature, mature and transitional forms in between. At 14 and 16 days of gestation, immature and transitional forms of DCs dominated. Mature cells increased significantly in number through late gestational days (18 days onwards). DCs (particularly mature and moderate mature forms) revealed signs of active phagocytosis manifested by the existence of cytoplasmic phagosomes and heterophagosomes. At 18 days of gestation as well as newborn liver mature DCs displayed two distinct morphological phenotypes according to the degree of development of either the smooth endoplasmic reticulum or the lysosomal compartment. Mature DCs delineated close appositions to other DCs, hepatocytes, and clustering with lymphocytes especially through their cellular processes. The features of phagocytosis and DC,T-cell contacts may signify a role of DCs in immune surveillance in the embryonic liver. [source] Modular Peptide Growth Factors for Substrate-Mediated Stem Cell Differentiation,ANGEWANDTE CHEMIE, Issue 34 2009Sam Lee Dr. Die Sequenzspezifität beim Binden eines modularen Peptidwachstumsfaktors (eBGa3) mit einer von BMP2 abgeleiteten Sequenz und einer durch Osteocalcin inspirierten Mineralbindesequenz an Ca-Ionen von Hydroxyapatit (HA) ist vermutlich teilweise auf die Entwicklung einer ,-helicalen Struktur in Gegenwart von HA zurückzuführen, durch die ,-carboxylierte Glutaminsäurereste im Peptid (cyan) von Ca-Atomen (orange) im HA-Kristallgitter registriert werden können. [source] Glioblastoma with Adipocyte-Like Tumor Cell Differentiation,Histological and Molecular Features of a Rare Differentiation PatternBRAIN PATHOLOGY, Issue 3 2009Christian H. Rickert Abstract We report on three adult patients with primary glioblastomas showing prominent adipocytic (lipomatous) differentiation, hence referred to as "glioblastomas with adipocyte-like tumor cell differentiation." Histologically, the tumors demonstrated typical features of glioblastoma but additionally contained areas consisting of glial fibrillary acidic protein (GFAP)-positive astrocytic tumor cells resembling adipocytes, that is, containing large intracellular lipid vacuoles. Comparative genomic hybridization (CGH) and focused molecular genetic analyses demonstrated gains of chromosomes 7, losses of chromosomes 9 and 10, as well as homozygous deletion of p14ARF in one of the tumors. The second tumor showed gains of chromosomes 3, 4, 8q and 12 as well as losses of chromosomes 10, 13, 15q, 19 and 22. In addition, this tumor carried homozygous deletions of CDKN2A and p14ARF as well as point mutations in the TP53 and PTEN genes. The third tumor also had a mutation in the PTEN gene. None of the tumors demonstrated EGFR, CDK4 or MDM2 amplification. Taken together, our results define a rare glioblastoma differentiation pattern and indicate that glioblastomas with adipocyte-like tumor cell differentiation share common molecular genetic features with other primary glioblastomas. [source] The role of stem cells in suppurative environmentsEXPERIMENTAL DERMATOLOGY, Issue 6 2006Dolores Herreros Purpose:,The management of suppurative perianal lesions presents an extremely challenging problem. Stem cells (SC) extracted from certain tissues, such as adipose tissue, can differentiate into various cell types. Therefore, we have tried to use such cells to stimulate healing in a purulent environment. Methods:,In the beginning, we designed a phase I clinical trial, involving five patients with Crohn's disease. We inoculated nine fistulas in four patients with autologous adipose-derived stem cells (ADSC) and were followed at least 8 weeks. Seventy-five percent became healed, and 25% showed a decrease in output flow. No adverse effects were observed in any patient. This study evidenced that such cells are safe. Then, we started a research line using SC in different suppurative environments. During the course of these studies, we had the opportunity to treat a patient with perianal hidradenitis suppurativa using our current protocol of ADSC transplantation. Eight weeks after injection, patient had no perianal suppuration, and a year later remains well. Discussion:,The biological mechanism that underlies the therapeutic success of ADSC transplantation is unknown. Cell differentiation, secretion of growth factors or immunomodulatory effects have been suggested. No ethical conflicts were identified by our Ethics Committee, because the cells were autologous. Conclusions:,Our study shows that ADSC are safe for the treatment of suppurative processes. The actual number of patients included and the uncontrolled nature of these pilot studies do not allow demonstration of the effectiveness of the treatment. However, the results encourage the performance of further studies. [source] In Vivo Function of a Differentiation Inhibitor, Id2IUBMB LIFE, Issue 4 2001Yoshifumi Yokota Abstract Cell differentiation is an essential process for the development of various cell types that constitute multicellular organisms. During development, the large family of factors bearing a helix-loop-helix (HLH) motif participates profoundly in this process and these factors serve as good experimental tools for investigating mechanisms underlying tissue-specific differentiation. The HLH family includes both positive and negative regulators of cell differentiation: basic HLH (bHLH)-type transcription factors and Id proteins, respectively. Following an exciting decade focusing on bHLH factors, advances achieved in studies of the inhibitory factors in the last couple of years have placed them in the front line of the research on differentiation and proliferation control. Here, we present and discuss recent results obtained using Id2 -deficient mice, which manifest intriguing phenotypes in various systems. [source] Cell differentiation and apoptosis of monocytic and promyelocytic leukemia cells (U-937 and HL-60) by tryptanthrin, an active ingredient of Polygonum tinctorium Lour.PATHOLOGY INTERNATIONAL, Issue 5 2001Tetsuo Kimoto Tryptanthrin, a bioactive ingredient of Polygonum tinctorium Lour., is a member of the Indigo plant family and has potent cytocidal effects on various human leukemia cells in vitro. At low concentrations, tryptanthrin enhanced the expression of cell differentiation (CD) markers in human monocytic (U-937) and promyelocytic (HL-60) leukemia cells indicative of differentiation to monocytes/macrophages. Furthermore, nitroblue tetrazolium (NBT) reductive and , -naphthyl butyrate esterase (NBE) activities were markedly increased after treatment. Tryptanthrin was more potent than dimethyl sulfoxide (DMSO) at inducing U-937 cell differentiation into monocytes/macrophages. After treatment with higher concentrations of tryptanthrin for 24 h, cytoplasmic vacuolation and destruction of mitochondria were observed. The leukemia cells died via apoptosis 48 h after treatment. Cytoplasmic vacuolation and apoptotic changes correlated with the dysfunction of mitochondria. Electron microscopic observations revealed marked swelling and destruction of mitochondria after exposure of the leukemia cells to tryptanthrin. Exposure to tryptanthrin enhanced Fas-induced apoptosis and increased caspase-3 activity before induction of apoptosis. These results show that low concentrations of tryptanthrin can induce differentiation of leukemia cells but higher concentrations will kill leukemia cells through apoptosis, possibly through a caspase-3/Fas antigen pathway. [source] Aging Adversely Impacts Biological Properties of Human Bone Marrow-derived Mesenchymal Stem Cells: Implications for Tissue Engineering Heart Valve ConstructionARTIFICIAL ORGANS, Issue 3 2010Yuan Xin Abstract Our aim was to study the aging effects on the in vitro biological properties of bone marrow-derived mesenchymal stem cells (BMSCs) for construction of tissue-engineered heart valves. BMSCs were taken from teenagers with congenital heart diseases, and middle-aged and elderly patients with valvular diseases. Proliferative abilities were compared among the three groups by using colony-forming unit counting and growth curves (5-bromo-2,-deoxyuridine assay). Cell differentiation, vascular endothelial growth factor (VEGF) release under hypoxic condition, and migratory abilities were compared as well. Colony-forming units in the teenage group were significantly greater than those in the other two groups (P < 0.05), and significantly higher counts were observed in the middle age group than in the aged group (P < 0.05). Growth curves presented similar trends in which cells' proliferative abilities in the aged group decreased significantly (P < 0.05), while no differences were noted between the two nonaged groups. The differentiation potential to endothelial cells, osteoblasts and adipocytes, VEGF releases, and migratory abilities differed significantly between the aged group and nonaged groups (P < 0.05). However, no differences were noted between the two nonaged groups. BMSCs from older patients with heart valve diseases could be harvested and expanded successfully, and the phenotype and morphology were uniform as nonaged groups. However, the proliferative and differentiation properties of aged cells, as well as cytokine release and migratory abilities, are significantly impaired. [source] Regulation of Human Skeletal Stem Cells Differentiation by Dlk1/Pref-1JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2004Basem M Abdallah Abstract Dlk-1/Pref-1 was identified as a novel regulator of human skeletal stem cell differentiation. Dlk1/Pref-1 is expressed in bone and cultured osteoblasts, and its constitutive overexpression led to inhibition of osteoblast and adipocyte differentiation of human marrow stromal cells. Introduction: Molecular control of human mesenchymal stem cell (hMSC) differentiation into osteoblasts and adipocytes is not known. In this study, we examined the role of delta-like 1/preadipocyte factor-1 (Dlk1/Pref-1) in regulating the differentiation of hMSCs. Materials and Methods: As a model for hMSCs, we have stably transduced telomerase-immortalized hMSC (hMSC-TERT) with the full length of human Dlk1/Pref-1 cDNA and tested its effect on hMSC growth and differentiation into osteoblasts or adipocytes as assessed by cytochemical staining, FACS analysis, and real time PCR. Ex vivo calvaria organ cultures assay was used to confirm the in vitro effect of Dlk/Pref-1 on bone formation. Results: Dlk1/Pref-1 was found to be expressed in fetal and adult bone, hMSCs, and some osteoblastic cell lines. A retroviral vector containing the human Dlk1/Pref-1 cDNA was used to create a cell line (hMSC-dlk1) expressing high levels of Dlk1/Pref-1 protein. Overexpression of Dlk1/Pref-1 did not affect the proliferation rate of hMSC, but the ability to form mature adipocytes, mineralized matrix in vitro, and new bone formation in neonatal murine calvariae organ cultures was reduced. These effects were associated with inhibition of gene expression markers of late stages of adipocyte (adipocyte fatty acid-binding protein [aP2], peroxisome proliferator-activated receptor-gamma2 [PPAR,2], and adiponectin [APM1]) and osteoblast differentiation (alkaline phosphatase [ALP], collagen type I [Col1], and osteocalcin [OC]). Lineage commitment markers for adipocytes (adipocyte determination and differentiation factor ,1 [ADD1]) and osteoblasts (core binding factor/runt-related binding factor 2 [Cbfa1/Runx2]) were not affected. Conclusion: During hMSC differentiation, Dlk1/Pref-1 maintains the size of the bipotential progenitor cell pool by inhibiting the formation of mature osteoblasts and adipocytes. [source] Architectural changes in the developing human brain based on the matrix cell theoryCONGENITAL ANOMALIES, Issue 3 2002Yasuhiro Nakamura ABSTRACT, Architectural changes in the developing human brain are discussed based on the matrix cell theory. Neural stem cells/matrix cells with self-renewing ability and multipotency exist in the developing human brain in vivo. The brain development is divided into three stages and the cell differentiation is time regulated. Immunohistochemical distribution of various markers for brain development is summarized and categorized along with differentiation lineages. Particularly, the existence of glial fibrillary acidic protein is re-evaluated in the developing human brain. The commonly used terms and concepts "radial glial fiber" or "subventricular zone" are also re-evaluated. [source] Human skeletal muscle cell differentiation is associated with changes in myogenic markers and enhanced insulin-mediated MAPK and PKB phosphorylationACTA PHYSIOLOGICA, Issue 4 2004L. Al-Khalili Abstract Aim:, We hypothesized that myogenic differentiation of HSMC would yield a more insulin responsive phenotype. Methods:, We assessed expression of several proteins involved in insulin action or myogenesis during differentiation of primary human skeletal muscle cultures (HSMC). Results:, Differentiation increased creatine kinase activity and expression of desmin and myocyte enhancer factor (MEF)2C. No change in expression was observed for big mitogen-activated protein kinase (BMK1/ERK5), MEF2A, insulin receptor (IR), hexokinase II, and IR substrates 1 and 2, while expression of glycogen synthase, extracellular signal-regulated kinase 1 and 2 (ERK1/2 MAP kinase) and the insulin responsive aminopeptidase increased after differentiation. In contrast to protein kinase B (PKB)a, expression of (PKB)b increased, with differentiation. Both basal and insulin-stimulated PI 3-kinase activity increased with differentiation. Insulin-mediated phosphorylation of PKB and ERK1/2 MAP kinase increased after differentiation. Conclusion:, Components of the insulin-signalling machinery are expressed in myoblast and myotube HSMC; however, insulin responsiveness to PKB and ERK MAP kinase phosphorylation increases with differentiation. [source] Myoblast attachment and spreading are regulated by different patterns by ubiquitous calpainsCYTOSKELETON, Issue 4 2006Germain Mazères Abstract The calcium-dependent proteolytic system is a large family of well-conserved ubiquitous and tissue-specific proteases, known as calpains, and an endogenous inhibitor, calpastatin. Ubiquitous calpains are involved in many physiological phenomena, such as the cell cycle, muscle cell differentiation, and cell migration. This study investigates the regulation of crucial steps of cell motility, myoblast adhesion and spreading, by calpains. Inhibition of each ubiquitous calpain isoform by antisense strategy pinpointed the involvement of each of these proteases in myoblast adhesion and spreading. Moreover, the actin cytoskeleton and microtubules were observed in transfected cells, demonstrating that each ubiquitous calpain could be involved in the actin fiber organization. C2C12 cells with reduced ,- or m-calpain levels have a rounded morphology and disorganized stress fibers, but no modification in the microtubule cytoskeleton. Antisense strategy directed against MARCKS, a calpain substrate during C2C12 migration, showed that this protein could play a role in stress fiber polymerization. A complementary proteomic analysis using C2C12 cells over-expressing calpastatin indicated that two proteins were under-expressed, while six, which are involved in the studied phenomena, were overexpressed after calpain inhibition. The possible role of these proteins in adhesion, spreading, and migration was discussed. Cell Motil. Cytoskeleton 63: 2006. © 2006 Wiley-Liss, Inc. [source] Epigenetic regulation in neural stem cell differentiationDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 6 2010Berry Juliandi The central nervous system (CNS) is composed of three major cell types , neurons, astrocytes, and oligodendrocytes , which differentiate from common multipotent neural stem cells (NSCs). This differentiation process is regulated spatiotemporally during the course of mammalian development. It is becoming apparent that epigenetic regulation is an important cell-intrinsic program, which can interact with transcription factors and environmental cues to modulate the differentiation of NSCs. This knowledge is important given the potential of NSCs to produce specific CNS cell types that will be beneficial for clinical applications. Here we review recent findings that address molecular mechanisms of epigenetic and transcription factor-mediated regulation that specify NSC fate during CNS development, with a particular focus on the developing mammalian forebrain. [source] Differentiation inducing factors in Dictyostelium discoideum: A novel low molecular factor functions at an early stage(s) of differentiationDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 9 2009Akiko A. Oohata There are reports that secreted factor(s) are involved in prespore cell differentiation in Dictyostelium discoideum, but the structures and functions of the various factors have not been elucidated. Previously, we described two prespore cell-inducing factors in conditioned medium; one was a glycoprotein named prespore cell-inducing factor (, factor, or PSI-1), and the other, a heat stable dialyzable factor(s). In the present paper, we purified and characterized the most potent prespore cell-inducing activity in dialysates. The factor began to be secreted after the onset of starvation and stopped being secreted once the cells had aggregated, which was earlier than the onset of the , factor gene expression. In addition, unlike , factor, its secretion did not appear to depend on activation of protein kinase A. Interestingly, the purified factor not only induced prespore cell specific genes such as pspA and cotC but also a prestalk-cell specific gene, ecmB in vitro. The purified factor is tentatively designated polyketide-like factor (PLF), because it seems to be a novel polyketide with 208 Da. Half maximal induction of prespore cell was obtained with 26 nmol/L of PLF. We propose that PLF plays a key role in the acquisition of differentiation commitment, before the , factor induces specifically prespore cell differentiation. [source] Sustained MAPK activation is dependent on continual NGF receptor regenerationDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 5 2004Dongru Qiu It still remains intriguing how signal specificity is achieved when different signals are relayed by the common intracellular signal transduction pathways. A well documented example for signal specificity determination is found in rat phaeochromocytoma PC12 cells where epidermal growth factor (EGF) stimulation produces a transient mitogen-activated protein kinase (MAPK) activation and leads to cell proliferation while nerve growth factor (NGF) initiates a sustained MAPK activation and induces cell differentiation. In this simulation, we demonstrated that NGF-induced sustained MAPK activation may mainly depend on continual regeneration of NGF receptors and that the presence of a small pool of surface receptors is enough to maintain a sustained MAPK activation. On the other hand, MAPK activation is not significantly sensitive to the half-life of internalized receptors and the levels of NGF-specific MAPK phosphatase MAP kinase phosphatase-3 (MKP-3), though cytoplasmic persistence of internalized NGF-bound receptors and the MKP-3 dependent feedback control also contribute to the sustaining of MAPK activation. These results are consistent with the recent experimental evidence that persistent tyrosine receptor kinase A (TrkA) activity is necessary to maintain transcription in the differentiating PC12 cells (Chang et al. 2003) and a sustained Src kinase activity is detected in response to NGF stimulation (Gatti 2003). It is suggested that sustained or transient MAPK activation induced by different growth factor and neurotrophins, which is crucial to their signaling specificity, could be satisfactorily accounted for by their specific receptor turnover kinetics rather than by the activation of specific downstream signaling cascades. [source] Identification and characterization of novel calcium-binding proteins of Dictyostelium and their spatial expression patterns during developmentDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 5-6 2003Haruyo Sakamoto Five putative Ca2+ -binding proteins, CBP5, 6, 7, 8 and 9, all having EF-hand motifs, were found by searching the Dictyostelium cDNA database (http://www.csm.biol.tsukuba.ac.jp/cDNAproject.html). 45Ca2+ -overlay experiments revealed that four of these (excluding CBP9) are real Ca2+ -binding proteins. Northern blot analysis revealed that the genes encoding CBP5, 6, 7 and 8 are all developmentally regulated. In situ hybridization analyses revealed that spatial expression of these genes was regulated in several different ways. CBP1, 2, 3, 5, 6 and 7 are expressed in prespore cells in the slug stage. Transcripts of the genes for CBP1 and 5 are enriched in prestalk subtype PstO cells. In contrast, CBP4 is expressed predominantly in PstO cells. CBP8 is evenly expressed at a very low level throughout the whole slug. Such distinct spatial expression patterns suggest that the CBP might be involved in morphogenesis and might have their own roles either in prespore or in prestalk cell differentiation of Dictyostelium. [source] Organ patterning in the adult stage: The role of Wnt/,-catenin signaling in liver zonation and beyondDEVELOPMENTAL DYNAMICS, Issue 1 2010Rolf Gebhardt Abstract Wnt/,-catenin signaling has been found to play key roles in metabolic zonation of adult liver, regeneration, and hepatocellular carcinogenesis. In this review, recent progress in this field is summarized, in particular the rapidly growing knowledge about the various interactions of ,-catenin with many transcription factors involved in controlling metabolism. These interactions may provide the basis for understanding how the wide range of activities of Wnt/,-catenin signaling is differentially interpreted. Based on these results, a three-level mode for the molecular interpretation of ,-catenin activity gradients in liver is proposed favoring cell differentiation, metabolic zonation, and proliferation. While derangement of the combinatorial interplay of the various transcription factors with ,-catenin at the intermediary activity level may contribute to the development of metabolic diseases, extremely high activation of ,-catenin may eventually lead to initiation and progression of hepatocellular tumors. Developmental Dynamics 239:45,55, 2010. © 2009 Wiley-Liss, Inc. [source] What drives cell morphogenesis: A look inside the vertebrate photoreceptorDEVELOPMENTAL DYNAMICS, Issue 9 2009Breandán Kennedy Abstract Vision mediating photoreceptor cells are specialized light-sensitive neurons in the outer layer of the vertebrate retina. The human retina contains approximately 130 million of such photoreceptors, which enable images of the external environment to be captured at high resolution and high sensitivity. Rod and cone photoreceptor subtypes are further specialized for sensing light in low and high illumination, respectively. To enable visual function, these photoreceptors have developed elaborate morphological domains for the detection of light (outer segments), for changing cell shape (inner segments), and for communication with neighboring retinal neurons (synaptic terminals). Furthermore, rod and cone subtypes feature unique morphological variations of these specialized characteristics. Here, we review the major aspects of vertebrate photoreceptor morphology and key genetic mechanisms that drive their formation. These mechanisms are necessary for cell differentiation as well as function. Their defects lead to cell death. Developmental Dynamics 238:2115,2138, 2009. © 2009 Wiley-Liss, Inc. [source] Early lens development in the zebrafish: A three-dimensional time-lapse analysisDEVELOPMENTAL DYNAMICS, Issue 9 2009Teri M.S. Greiling Abstract In vivo, high-resolution, time-lapse imaging characterized lens development in the zebrafish from 16 to 96 hr postfertilization (hpf). In zebrafish, the lens placode appeared in the head ectoderm, similar to mammals. Delamination of the surface ectoderm resulted in the formation of the lens mass, which progressed to a solid sphere of cells separating from the developing cornea at approximately 24 hpf. A lens vesicle was not observed and apoptosis was not a major factor in separation of the lens from the future cornea. Differentiation of primary fibers began in the lens mass followed by formation of the anterior epithelium after delamination was complete. Secondary fibers differentiated from elongating epithelial cells near the posterior pole. Quantification characterized three stages of lens growth. The study confirmed the advantages of live-cell imaging for three-dimensional quantitative structural characterization of the mechanism(s) responsible for cell differentiation in formation of a transparent, symmetric, and refractile lens. Developmental Dynamics 238:2254,2265, 2009. © 2009 Wiley-Liss, Inc. [source] Chondrocyte-specific Smad4 gene conditional knockout results in hearing loss and inner ear malformation in miceDEVELOPMENTAL DYNAMICS, Issue 8 2009Shi-Ming Yang Abstract Smad4 is the central intracellular mediator of transforming growth factor-, (TGF-,) signaling, which plays crucial roles in tissue regeneration, cell differentiation, embryonic development, and regulation of the immune system. Conventional Smad4 gene knockout results in embryonic lethality, precluding its use in studies of the role of Smad4 in inner ear development. We used chondrocyte-specific Smad4 knockout mice (Smad4Co/Co) to investigate the function of Smad4 in inner ear development. Smad4Co/Co mice were characterized by a smaller cochlear volume, bone malformation, and abnormalities of the osseous spiral lamina and basilar membrane. The development of the hair cells was also abnormal, as evidenced by the disorganized stereocilia and reduced density of the neuronal processes beneath the hair cells. Auditory function tests revealed the homozygous Smad4Co/Co mice suffered from severe sensorineural hearing loss. Our results suggest that Smad4 is required for inner ear development and normal auditory function in mammals. Developmental Dynamics, 2009. © 2009 Wiley-Liss, Inc. [source] Role for notch signaling in salivary acinar cell growth and differentiationDEVELOPMENTAL DYNAMICS, Issue 3 2009Howard Dang Abstract The Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. The Notch signaling is essential for Drosophila salivary gland development but its role in mammalian salivary gland remains unclear. The human salivary epithelial cell line, HSG, was studied to determine the role of Notch signaling in salivary epithelial cell differentiation. HSG expressed Notch 1 to 4, and the Notch ligands Jagged 1 and 2 and Delta 1. Treatment of HSG cells with inhibitors of ,-secretase, which is required for Notch cleavage and activation, blocked vimentin and cystatin S expression, an indicator of HSG differentiation. HSG differentiation was also associated with Notch downstream signal Hes-1 expression, and Hes-1 expression was inhibited by ,-secretase inhibitors. siRNA corresponding to Notch 1 to 4 was used to show that silencing of all four Notch receptors was required to inhibit HSG differentiation. Normal human submandibular gland expressed Notch 1 to 4, Jagged 1 and 2, and Delta 1, with nuclear localization indicating Notch signaling in vivo. Hes-1 was also expressed in the human tissue, with staining predominantly in the ductal cells. In salivary tissue from rats undergoing and recovering from ductal obstruction, we found that Notch receptors and ligands were expressed in the nucleus of the regenerating epithelial cells. Taken together, these data suggest that Notch signaling is critical for normal salivary gland cell growth and differentiation. Developmental Dynamics 238:724,731, 2009. © 2009 Wiley-Liss, Inc. [source] Analysis of human muscle stem cells reveals a differentiation-resistant progenitor cell population expressing Pax7 capable of self-renewalDEVELOPMENTAL DYNAMICS, Issue 1 2009Bradley Pawlikowski Abstract Studies using mouse models have established a critical role for resident satellite stem cells in skeletal muscle development and regeneration, but little is known about this paradigm in human muscle. Here, using human muscle stem cells, we address their lineage progression, differentiation, migration, and self-renewal. Isolated human satellite cells expressed ,7-integrin and other definitive muscle markers, were highly motile on laminin substrates and could undergo efficient myotube differentiation and myofibrillogenesis. However, only a subpopulation of the myoblasts expressed Pax7 and displayed a variable lineage progression as measured by desmin and MyoD expression. Analysis identified a differentiation-resistant progenitor cell population that was Pax7+/desmin, and capable of self-renewal. This study extends our understanding of the role of Pax7 in regulating human satellite stem cell differentiation and self-renewal. Developmental Dynamics 238:138,149, 2009. © 2008 Wiley-Liss, Inc. [source] Relationship between delta-like and proneural bHLH genes during chick retinal developmentDEVELOPMENTAL DYNAMICS, Issue 6 2008Branden R. Nelson Abstract Notch signaling in the retina maintains a pool of progenitor cells throughout retinogenesis. However, two Notch-ligands from the Delta-like gene family, Dll1 and Dll4, are present in the developing retina. To understand their relationship, we characterized Dll1 and Dll4 expression with respect to proliferating progenitor cells and newborn neurons in the chick retina. Dll4 matched the pattern of neural differentiation. By contrast, Dll1 was primarily expressed in progenitor cells. We compared Dll1 and Dll4 kinetic profiles with that of the transiently up-regulated cascade of proneural basic helix,loop,helix (bHLH) genes after synchronized progenitor cell differentiation, which suggested a potential role for Ascl1 in the regulation of Delta-like genes. Gain-of-function assays demonstrate that Ascl1 does influence Delta-like gene expression and Notch signaling activity. These data suggest that multiple sources of Notch signaling from newborn neurons and progenitors themselves coordinate retinal histogenesis. Developmental Dynamics 237:1565,1580, 2008. © 2008 Wiley-Liss, Inc. [source] WNT signaling affects gene expression in the ventral diencephalon and pituitary gland growthDEVELOPMENTAL DYNAMICS, Issue 4 2008Mary Anne Potok Abstract We examined the role of WNT signaling in pituitary development by characterizing the pituitary phenotype of three WNT knockout mice and assessing the expression of WNT pathway components. Wnt5a mutants have expanded domains of Fgf10 and bone morphogenetic protein expression in the ventral diencephalon and a reduced domain of LHX3 expression in Rathke's pouch. Wnt4 mutants have mildly reduced cell differentiation, reduced POU1F1 expression, and mild anterior lobe hypoplasia. Wnt4, Wnt5a double mutants exhibit an additive pituitary phenotype of dysmorphology and mild hypoplasia. Wnt6 mutants have no obvious pituitary phenotype. We surveyed WNT expression and identified transcripts for numerous Wnts, Frizzleds, and downstream pathway members in the pituitary and ventral diencephalon. These findings support the emerging model that WNT signaling affects the pituitary gland via effects on ventral diencephalon signaling, and suggest additional Wnt genes that are worthy of functional studies. Developmental Dynamics 237:1006,1020, 2008. © 2008 Wiley-Liss, Inc. [source] Extrinsic versus intrinsic cues in avian paraxial mesoderm patterning and differentiationDEVELOPMENTAL DYNAMICS, Issue 9 2007Ingo Bothe Abstract Somitic and head mesoderm contribute to cartilage and bone and deliver the entire skeletal musculature. Studies on avian somite patterning and cell differentiation led to the view that these processes depend solely on cues from surrounding tissues. However, evidence is accumulating that some developmental decisions depend on information within the somitic tissue itself. Moreover, recent studies established that head and somitic mesoderm, though delivering the same tissue types, are set up to follow their own, distinct developmental programmes. With a particular focus on the chicken embryo, we review the current understanding of how extrinsic signalling, operating in a framework of intrinsically regulated constraints, controls paraxial mesoderm patterning and cell differentiation. Developmental Dynamics 236:2397,2409, 2007. © 2007 Wiley-Liss, Inc. [source] Disruption of fibroblast growth factor receptor 3 signaling results in defects in cellular differentiation, neuronal patterning, and hearing impairment,DEVELOPMENTAL DYNAMICS, Issue 7 2007Chandrakala Puligilla Abstract Deletion of fibroblast growth factor receptor 3 (Fgfr3) leads to hearing impairment in mice due to defects in the development of the organ of Corti, the sensory epithelium of the Cochlea. To examine the role of FGFR3 in auditory development, cochleae from Fgfr3,/, mice were examined using anatomical and physiological methods. Deletion of Fgfr3 leads to the absence of inner pillar cells and an increase in other cell types, suggesting that FGFR3 regulates cell fate. Defects in outer hair cell differentiation were also observed and probably represent the primary basis for hearing loss. Furthermore, innervation defects were detected consistent with changes in the fiber guidance properties of pillar cells. To elucidate the mechanisms underlying the effects of FGFR3, we examined the expression of Bmp4, a known target. Bmp4 was increased in Fgfr3,/, cochleae, and exogenous application of bone morphogenetic protein 4 (BMP4) onto cochlear explants induced a significant increase in the outer hair cells, suggesting the Fgf and Bmp signaling act in concert to pattern the cochlea. Developmental Dynamics 236:1905,1917, 2007. Published 2007 Wiley-Liss, Inc. [source] Zac1 promotes a Müller glial cell fate and interferes with retinal ganglion cell differentiation in Xenopus retinaDEVELOPMENTAL DYNAMICS, Issue 1 2007Lin Ma Abstract The timing of cell cycle exit is tightly linked to cell fate specification in the developing retina. Accordingly, several tumor suppressor genes, which are key regulators of cell cycle exit in cancer cells, play critical roles in retinogenesis. Here we investigated the role of Zac1, a tumor suppressor gene encoding a zinc finger transcription factor, in retinal development. Strikingly, in gain-of-function assays in Xenopus, mouse Zac1 promotes proliferation and apoptosis at an intermediate stage of retinogenesis. Zac1 also influences cell fate decisions, preferentially promoting the differentiation of tumor-like clusters of abnormal neuronal cells in the ganglion cell layer, as well as inducing the formation of supernumerary Müller glial cells at the expense of other cell types. Thus Zac1 has the capacity to influence cell cycle exit, and cell fate specification and differentiation decisions by retinal progenitors, suggesting that further functional studies will uncover new insights into how retinogenesis is regulated. Developmental Dynamics 236:192,202, 2007. © 2006 Wiley-Liss, Inc. [source] GATA-4 is required for sex steroidogenic cell development in the fetal mouseDEVELOPMENTAL DYNAMICS, Issue 1 2007Malgorzata Bielinska Abstract The transcription factor GATA-4 is expressed in Sertoli cells, steroidogenic Leydig cells, and other testicular somatic cells. Previous studies have established that interaction between GATA-4 and its cofactor FOG-2 is necessary for proper Sry expression and all subsequent steps in testicular organogenesis, including testis cord formation and differentiation of both Sertoli and fetal Leydig cells. Since fetal Leydig cell differentiation depends on Sertoli cell,derived factors, it has remained unclear whether GATA-4 has a cell autonomous role in Leydig cell development. We used two experimental systems to explore the role of GATA-4 in the ontogeny of testicular steroidogenic cells. First, chimeric mice were generated by injection of Gata4,/, ES cells into Rosa26 blastocysts. Analysis of the resultant chimeras showed that in developing testis Gata4,/, cells can contribute to fetal germ cells and interstitial fibroblasts but not fetal Leydig cells. Second, wild-type or Gata4,/, ES cells were injected into the flanks of intact or gonadectomized nude mice and the resultant teratomas examined for expression of steroidogenic markers. Wild-type but not Gata4,/, ES cells were capable of differentiating into gonadal-type steroidogenic lineages in teratomas grown in gonadectomized mice. In chimeric teratomas derived from mixtures of GFP-tagged Gata4+/+ ES cells and unlabeled Gata4,/, ES cells, sex steroidogenic cell differentiation was restricted to GFP-expressing cells. Collectively these data suggest that GATA-4 plays an integral role in the development of testicular steroidogenic cells. Developmental Dynamics 236:203,213, 2007. © 2006 Wiley-Liss, Inc. [source] Divergent roles of the DEAD-box protein BS-PL10, the urochordate homologue of human DDX3 and DDX3Y proteins, in colony astogeny and ontogenyDEVELOPMENTAL DYNAMICS, Issue 6 2006Amalia Rosner Abstract Proteins of the highly conserved PL-10 (Ded1P) subfamily of DEAD-box family, participate in a wide variety of biological functions. However, the entire spectrum of their functions in both vertebrates and invertebrates is still unknown. Here, we isolated the Botryllus schlosseri (Urochordata) homologue, BS-PL10, revealing its distributions and functions in ontogeny and colony astogeny. In botryllid ascidians, the colony grows by increasing the number of modular units (each called a zooid) through a whole colony synchronized and weekly cyclical astogenic budding process (blastogenesis). At the level of the colony, both BS-PL10 mRNA and its protein (78 kDa) fluctuate in a weekly pattern that corresponds with the animal's blastogenic cycle, increasing from blastogenic stage A to blastogenic stage D. At the organ/module level, a sharp decline is revealed. Primary and secondary developing buds express high levels of BS-PL10 mRNA and protein at all blastogeneic stages. These levels are reduced four to nine times in the new set of functional zooids. This portrait of colony astogeny differed from its ontogeny. Oocytes and sperm cells express high levels of BS-PL10 protein only at early stages of development. Young embryos reveal background levels with increased expressions in some organs at more developed stages. Results reveal that higher levels of BS-PL10 mRNA and protein are characteristic to multipotent soma and germ cells, but patterns deviate between two populations of differentiating stem cells, the stem cells involved in weekly blastogenesis and stem cells involved in embryogenesis. Two types of experimental manipulations, zooidectomy and siRNA assays, have confirmed the importance of BS-PL10 for cell differentiation and organogenesis. BS-PL10 (phylogenetically matching the animal's position in the evolutionary tree), is the only member of this subfamily in B. schlosseri, featuring a wide range of biological activities, some of which represent pivotal roles. The surprising weekly cyclical expression and the participation in cell differentiation posit this molecule as a model system for studying PL10 protein subfamily. Developmental Dynamics 235:1508,1521, 2006. © 2006 Wiley-Liss, Inc. [source] In vivo and in vitro analysis of the vasculogenic potential of avian proepicardial and epicardial cells,DEVELOPMENTAL DYNAMICS, Issue 4 2006Juan A. Guadix Abstract Coronary vessel formation is a special case in the context of embryonic vascular development. A major part of the coronary cellular precursors (endothelial, smooth muscle, and fibroblastic cells) derive from the proepicardium and the epicardium in what can be regarded as a late event of angioblastic and smooth muscle cell differentiation. Thus, coronary morphogenesis is dependent on the epithelial,mesenchymal transformation of the proepicardium and the epicardium. In this study, we present several novel observations about the process of coronary vasculogenesis in avian embryos, namely: (1) The proepicardium displays a high vasculogenic potential, both in vivo (as shown by heterotopic transplants) and in vitro, which is modulated by vascular endothelial growth factor (VEGF) and basic fibroblast growth factor signals; (2) Proepicardial and epicardial cells co-express receptors for platelet-derived growth factor-BB and VEGF; (3) Coronary angioblasts (found all through the epicardial, subepicardial, and compact myocardial layers) express the Wilms' tumor associated transcription factor and the retinoic acid-synthesizing enzyme retinaldehyde-dehydrogenase-2, two markers of the coelomic epithelium involved in coronary endothelium development. All these results contribute to the development of our knowledge on the vascular potential of proepicardial/epicardial cells, the existent interrelationships between the differentiating coronary cell lineages, and the molecular mechanisms involved in the regulation of coronary morphogenesis. Developmental Dynamics 235:1014,1026, 2006. © 2006 Wiley-Liss, Inc. [source] Macroarray-based analysis of tail regeneration in Xenopus laevis larvae,DEVELOPMENTAL DYNAMICS, Issue 4 2005Akira Tazaki Abstract Xenopus larvae possess a remarkable ability to regenerate their tails after they have been severed. To gain an understanding of the molecular mechanisms underlying tail regeneration, we performed a cDNA macroarray-based analysis of gene expression. A Xenopus cDNA macroarray representing 42,240 independent clones was differentially hybridized with probes synthesized from the total RNA of normal and regenerating tails. Temporal expression analysis revealed that the up-regulated genes could be grouped into early or late responding genes. A comparative expression analysis revealed that most genes showed similar expression patterns between tail development and regeneration. However, some genes showed regeneration-specific expression. Finally, we identified 48 up-regulated genes that fell into several categories based on their putative functions. These categories reflect the various processes that take place during regeneration, such as inflammation response, wound healing, cell proliferation, cell differentiation, and control of cell structure. Thus, we have identified a panel of genes that appear to be involved in the process of regeneration. Developmental Dynamics 233:1394,1404, 2005. © 2005 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||||||||