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Fate Determination (fate + determination)
Kinds of Fate Determination Selected AbstractsXenopus axin-related protein: A link between its centrosomal localization and function in the Wnt/,-catenin pathwayDEVELOPMENTAL DYNAMICS, Issue 1 2010Evguenia M. Alexandrova Abstract The Wnt/,-catenin signaling pathway regulates cell proliferation and cell fate determination in multiple systems. However, the subcellular localization of Wnt pathway components and the significance of this localization for the pathway regulation have not been extensively analyzed. Here we report that Xenopus Axin-related protein (XARP), a component of the ,-catenin destruction complex, is localized to the centrosome. This localization of XARP requires the presence of the DIX domain and an adjacent region. Since other components of the Wnt pathway have also been shown to associate with the centrosome, we tested a hypothesis that the ,-catenin destruction complex operates at the centrosome. However, XARP mutants with poor centrosomal localization revealed an enhanced rather than decreased ability to antagonize the Wnt/,-catenin pathway. Our data are consistent with the idea that the inactivation of XARP at the centrosome is an important regulatory point in Wnt signaling. Developmental Dynamics 239:261,270, 2010. © 2009 Wiley-Liss, Inc. [source] Recent advances in craniofacial morphogenesisDEVELOPMENTAL DYNAMICS, Issue 9 2006Yang Chai Abstract Craniofacial malformations are involved in three fourths of all congenital birth defects in humans, affecting the development of head, face, or neck. Tremendous progress in the study of craniofacial development has been made that places this field at the forefront of biomedical research. A concerted effort among evolutionary and developmental biologists, human geneticists, and tissue engineers has revealed important information on the molecular mechanisms that are crucial for the patterning and formation of craniofacial structures. Here, we highlight recent advances in our understanding of evo,devo as it relates to craniofacial morphogenesis, fate determination of cranial neural crest cells, and specific signaling pathways in regulating tissue,tissue interactions during patterning of craniofacial apparatus and the morphogenesis of tooth, mandible, and palate. Together, these findings will be beneficial for the understanding, treatment, and prevention of human congenital malformations and establish the foundation for craniofacial tissue regeneration. Developmental Dynamics 235:2353,2375, 2006. © 2006 Wiley-Liss, Inc. [source] Foxg1 is required for morphogenesis and histogenesis of the mammalian inner earDEVELOPMENTAL DYNAMICS, Issue 9 2006Sarah Pauley Abstract The forkhead genes are involved in patterning, morphogenesis, cell fate determination, and proliferation. Several Fox genes (Foxi1, Foxg1) are expressed in the developing otocyst of both zebrafish and mammals. We show that Foxg1 is expressed in most cell types of the inner ear of the adult mouse and that Foxg1 mutants have both morphological and histological defects in the inner ear. These mice have a shortened cochlea with multiple rows of hair cells and supporting cells. Additionally, they demonstrate striking abnormalities in cochlear and vestibular innervation, including loss of all crista neurons and numerous fibers that overshoot the organ of Corti. Closer examination shows that some anterior crista fibers exist in late embryos. Tracing these fibers shows that they do not project to the brain but, instead, to the cochlea. Finally, these mice completely lack a horizontal crista, although a horizontal canal forms but comes off the anterior ampulla. Anterior and posterior cristae, ampullae, and canals are reduced to varying degrees, particularly in combination with Fgf10 heterozygosity. Compounding Fgf10 heterozygotic effects suggest an additive effect of Fgf10 on Foxg1, possibly mediated through bone morphogenetic protein regulation. We show that sensory epithelia formation and canal development are linked in the anterior and posterior canal systems. Much of the Foxg1 phenotype can be explained by the participation of the protein binding domain in the delta/notch/hes signaling pathway. Additional Foxg1 effects may be mediated by the forkhead DNA binding domain. Developmental Dynamics 235:2470,2482, 2006. © 2006 Wiley-Liss, Inc. [source] Differential expression of polycomb repression complex 1 (PRC1) members in the developing mouse brain reveals multiple complexesDEVELOPMENTAL DYNAMICS, Issue 9 2006Tanja Vogel Abstract Polycomb group (PcG) genes are regulators of body segmentation and cell growth, therefore being important players during development. PcG proteins form large complexes (PRC) that fulfil mostly repressive regulative functions on homeotic gene expression. Although expression of PcG genes in the brain has been noticed, the involvement of PcG genes in the processes of brain development is not understood. In this study, we analysed the expression patterns of PRC1 complex members to reveal PcG proteins that might be relevant for mouse brain development. Using in situ hybridisation, we show PRC1 activity in proliferative progenitor cells during neurogenesis, but also in maturated neuronal structures. PRC1 complex compositions vary in a spatial and temporal controlled manner during mouse brain development, providing cellular tools to act in different developmental contexts of cell proliferation, cell fate determination, and differentiation. Developmental Dynamics 235:2574,2585, 2006. © 2006 Wiley-Liss, Inc. [source] Dlk1 expression marks developing endothelium and sites of branching morphogenesis in the mouse embryo and placentaDEVELOPMENTAL DYNAMICS, Issue 4 2006Aleksey Yevtodiyenko Abstract The protein product of the Delta-like 1 (Dlk1) gene belongs to the Delta-Notch family of signaling molecules, proteins involved in cell fate determination in many tissues during development. The DLK1 protein is believed to function as a growth factor, maintaining the proliferative state of undifferentiated cells, and is usually down-regulated as immature cells differentiate. The expression pattern of the DLK1 protein has been described in certain human tissues; however, Dlk1 expression is not well understood in the mouse, the most tractable mammalian genetic model system. To better understand the role of Dlk1 in embryonic development, the tissue-specific expression pattern of Dlk1 mRNA during mouse embryogenesis was analyzed by in situ hybridization. In embryonic day 12.5 (e12.5) embryos, high levels of Dlk1 were found in the developing pituitary, pancreas, lung, adrenal, and many mesodermally derived tissues. Strikingly, Dlk1 expression also marks the growing branches of organs that develop through the process of branching morphogenesis. At e16.5, Dlk1 expression is down-regulated in most tissues but remains in the pituitary, the adrenal gland, and in skeletal muscle. In the placenta, expression of Dlk1 is detected in endothelial cells lining the fetal blood vessels of the labyrinth. This pattern is distinct from that seen in the human placenta and suggests a role for Dlk1 in regulating maternal,fetal interactions. Developmental Dynamics 235:1115,1123, 2006. © 2006 Wiley-Liss, Inc. [source] Phenotypic analyses of mouse embryos with ubiquitous expression of Oct4: Effects on mid,hindbrain patterning and gene expressionDEVELOPMENTAL DYNAMICS, Issue 1 2005Verónica Ramos-Mejía Abstract Oct4 is a transcription factor that has been associated with pluripotency and fate determination in the initial cell lineages of mammals. On the other hand, Pou2, the ortholog of Oct4 in zebrafish, serves additional later functions during brain development acting as a differentiation switch. In mice, Oct4 is expressed throughout the neural plate of embryos until embryonic day (E) 8.0. In this study, we produced transgenic mouse embryos that ubiquitously express Oct4 and analyzed the consequences during development. We show that, at E8.0, a higher dosage of Oct4 in the neuroectoderm is sufficient to transiently alter mid,hindbrain patterning and produced a strong up-regulation of Pax2, indicating that Oct4 can regulate this gene in vivo. After E9.5, ectopic Oct4 in this region produced cell death and affected the development of the forebrain, suggesting that, at these later stages, Oct4 down-regulation is necessary for normal development to proceed. The phenotype of the transgenic embryos was also accompanied with an increase of Fgf8 expression in several of its endogenous domains, suggesting the possibility that Oct4 can participate in the regulation of expression of this ligand. Our observations support the hypothesis that Oct4, like zebrafish Pou2, has a conserved function during early brain patterning in mouse. Developmental Dynamics 232:180,190, 2005. © 2004 Wiley-Liss, Inc. [source] The essential haematopoietic transcription factor Scl is also critical for neuronal developmentEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2006Cara K. Bradley Abstract The basic helix-loop-helix (bHLH) transcription factor Scl displays tissue-restricted expression and is critical for the establishment of the haematopoietic system; loss of Scl results in embryonic death due to absolute anaemia. Scl is also expressed in neurons of the mouse diencephalon, mesencephalon and metencephalon; however, its requirement in those sites remains to be determined. Here we report conditional deletion of Scl in neuronal precursor cells using the Cre/LoxP system. Neuronal-Scl deleted mice died prematurely, were growth retarded and exhibited an altered motor phenotype characterized by hyperactivity and circling. Moreover, ablation of Scl in the nervous system affected brain morphology with abnormal neuronal development in brain regions known to express Scl under normal circumstances; there was an almost complete absence of Scl-null neurons in the hindbrain and partial loss of Scl-null neurons in the thalamus and midbrain from early neurogenesis onwards. Our results demonstrate a crucial role for Scl in the development of Scl-expressing neurons, including ,-aminobutyric acid (GABA)ergic interneurons. Our study represents one of the first demonstrations of functional overlap of a single bHLH protein that regulates neural and haematopoietic cell development. This finding underlines Scl's critical function in cell fate determination of mesodermal as well as neuroectodermal tissues. [source] Generation of embryonic stem cells and transgenic mice expressing green fluorescence protein in midbrain dopaminergic neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2004Suling Zhao Abstract We have generated embryonic stem (ES) cells and transgenic mice with green fluorescent protein (GFP) inserted into the Pitx3 locus via homologous recombination. In the central nervous system, Pitx3 -directed GFP was visualized in dopaminergic (DA) neurons in the substantia nigra and ventral tegmental area. Live primary DA neurons can be isolated by fluorescence-activated cell sorting from these transgenic mouse embryos. In culture, Pitx3,GFP is coexpressed in a proportion of ES-derived DA neurons. Furthermore, ES cell-derived Pitx3,GFP expressing DA neurons responded to neurotrophic factors and were sensitive to DA-specific neurotoxin N-4-methyl-1, 2, 3, 6-tetrahydropyridine. We anticipate that the Pitx3,GFP ES cells could be used as a powerful model system for functional identification of molecules governing mDA neuron differentiation and for preclinical research including pharmaceutical drug screening and transplantation. The Pitx3 knock-in mice, on the other hand, could be used for purifying primary neurons for molecular studies associated with the midbrain-specific DA phenotype at a level not previously feasible. These mice would also provide a useful tool to study DA fate determination from embryo- or adult-derived neural stem cells. [source] Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylationGENES TO CELLS, Issue 7 2009Meixiang Sang Plk3, one of Polo-like kinase family members, is involved in the regulation of cell cycle progression and DNA damage response. In this study, we found that Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation. During cisplatin (CDDP)-mediated apoptosis, Plk3 was transcriptionally induced, whereas its protein level was kept at basal level, suggesting that Plk3 might rapidly degrade in response to CDDP. Immunoprecipitation and in vitro pull-down experiments demonstrated that Plk3 interacts with p73. Luciferase reporter assays and RT-PCR experiments revealed that Plk3 inhibits p73-mediated transcriptional activity. Consistent with these results, pro-apoptotic activity of p73 was blocked by Plk3. Additionally, Plk3 decreased the stability of p73. Intriguingly, kinase-deficient Plk3 failed to inhibit p73 function, indicating that kinase activity of Plk3 is required for Plk3-mediated inhibition of p73. Indeed, in vitro kinase reaction showed that NH2 -terminal portion of p73 is phosphorylated by Plk3. In accordance with these observations, knocking down of Plk3 increased the stability of p73 and promoted CDDP-mediated apoptosis in association with up-regulation of p73. Collectively, our present findings suggest that Plk3 plays an important role in the regulation of cell fate determination in response to DNA damage through the inhibition of p73. [source] Generation of spinal motor neurons from human fetal brain-derived neural stem cells: Role of basic fibroblast growth factorJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2009Paivi M. Jordan Abstract Neural stem cells (NSCs) have some specified properties but are generally uncommitted and so can change their fate after exposure to environmental cues. It is unclear to what extent this NSC plasticity can be modulated by extrinsic cues and what are the molecular mechanisms underlying neuronal fate determination. Basic fibroblast growth factor (bFGF) is a well-known mitogen for proliferating NSCs. However, its role in guiding stem cells for neuronal subtype specification is undefined. Here we report that in-vitro-expanded human fetal forebrain-derived NSCs can generate cholinergic neurons with spinal motor neuron properties when treated with bFGF within a specific time window. bFGF induces NSCs to express the motor neuron marker Hb9, which is blocked by specific FGF receptor inhibitors and bFGF neutralizing antibodies. This development of spinal motor neuron properties is independent of selective proliferation or survival and does not require high levels of MAPK activation. Thus our study indicates that bFGF can play an important role in modulating plasticity and neuronal fate of human NSCs and presumably has implications for exploring the full potential of brain NSCs for clinical applications, particularly in spinal motor neuron regeneration. © 2008 Wiley-Liss, Inc. [source] Cell fate transitions during stomatal developmentBIOESSAYS, Issue 8 2009Laura Serna Abstract Stomata, the most influential components in gas exchange with the atmosphere, represent a revealing system for studying cell fate determination. Studies in Arabidopsis thaliana have demonstrated that many of the components, functioning in a signaling cascade, guide numerous cell fate transitions that occur during stomatal development. The signaling cascade is initiated at the cell surface through the activation of the membrane receptors TOO MANY MOUTHS (TMM) and/or ERECTA (ER) family members by the secretory peptide EPIDERMAL PATTERNING FACTOR1 (EPF1) and/or a substrate processed proteolytically by the subtilase STOMATAL DENSITY AND DISTRIBUTION1 (SDD1) and transduced through cytoplasmic MAP kinases (YODA (YDA), MKK4/MKK5, and MPK3/MPK6) towards the nucleus. In the nucleus, these MAP kinases regulate the activity of the basic helix-loop-helix (bHLH) proteins SPEECHLESS (SPCH), MUTE, and FAMA, which act in concert with the bHLH-Leu zipper protein SCREAM (SCRM) (and/or its closely related paralog, SCREAM2). This article reviews current insights into the role of this signaling cascade during stomatal development. [source] Early mouse embryo development: could epigenetics influence cell fate determination?BIOESSAYS, Issue 6 2007Amandine Henckel It is generally assumed that the developmental program of embryogenesis relies on epigenetic mechanisms. However, a mechanistic link between epigenetic marks and cell fate decisions had not been established so far. In a recent article, Torres-Padilla and colleagues1 show that epigenetic information and, more precisely, histone arginine methylation mediated by CARM1 could contribute to cell fate decisions in the mouse 4-cell-stage embryo. It provides the first indications that global epigenetic information influences allocation of pluripotent cells toward the first cell lineages. BioEssays 29:520,524, 2007. © 2007 Wiley Periodicals, Inc. [source] Controlling the stem cell niche: right time, right place, right strengthBIOESSAYS, Issue 1 2006Catherin Niemann Wnt signalling through ,-catenin plays a pivotal role during embryonic pattern formation, cell fate determination and tissue homeostasis in the adult organism. In the skin, as in many other tissues, Wnt/,-catenin signalling can control lineage determination and differentiation. However, it was not known whether Wnt/,-catenin signalling is an immediate regulator of the stem cell niche in skin tissue. A recent publication now provides evidence that Wnt/,-catenin signalling exerts a direct effect on the stem cell compartment by inducing quiescent stem cells to enter the cell cycle during early stages of hair follicle regeneration. In addition, the authors demonstrate that ,-catenin is required for maintenance of the stem cell pool in the tissue.1 The data suggest that a gradient in Wnt/,-catenin activity levels can induce different responses within distinct cell populations reflected by activation of distinct transcriptional profiles. BioEssays 28:1,5, 2006. © 2005 Wiley Periodicals, Inc. [source] Turning it up a Notch: cross-talk between TGF, and Notch signalingBIOESSAYS, Issue 2 2005Michael Klüppel Signaling through both the transforming growth factor , (TGF,) superfamily of growth factors and Notch play crucial roles during embryonic pattern formation and cell fate determination. Although both pathways are able to exert similar biological responses in certain cell types, a functional interaction between these two signaling pathways has not been described. Now, three papers provide evidence of both synergy and antagonism between TGF, and Notch signaling.1,3 These reports describe a requirement for Notch signal transducers in TGF,- and BMP-induced expression of Notch target genes, as well as in BMP-controlled cell differentiation and migration. These papers uncover a direct link between the Notch and TGF, pathways and suggest a critical role for Notch in some of the biological responses to TGF, family signaling. BioEssays 27:115,118, 2005. © 2005 Wiley Periodicals, Inc. [source] Epigenetics and T helper 1 differentiationIMMUNOLOGY, Issue 3 2009Thomas M. Aune Summary Naïve T helper cells differentiate into two subsets, T helper 1 and 2, which either transcribe the Ifng gene and silence the Il4 gene or transcribe the Il4 gene and silence the Ifng gene, respectively. This process is an essential feature of the adaptive immune response to a pathogen and the development of long-lasting immunity. The ,histone code' hypothesis proposes that formation of stable epigenetic histone marks at a gene locus that activate or repress transcription is essential for cell fate determinations, such as T helper 1/T helper 2 cell fate decisions. Activation and silencing of the Ifng gene are achieved through the creation of stable epigenetic histone marks spanning a region of genomic DNA over 20 times greater than the gene itself. Key transcription factors that drive the T helper 1 lineage decision, signal transducer and activator 4 (STAT4) and T-box expressed in T cells (T-bet), play direct roles in the formation of activating histone marks at the Ifng locus. Conversely, STAT6 and GATA binding protein 3, transcription factors essential for the T helper 2 cell lineage decision, establish repressive histone marks at the Ifng locus. Functional studies demonstrate that multiple genomic elements up to 50 kilobases from Ifng play critical roles in its proper transcriptional regulation. Studies of three-dimensional chromatin conformation indicate that these distal regulatory elements may loop towards Ifng to regulate its transcription. We speculate that these complex mechanisms have evolved to tightly control levels of interferon-, production, given that too little or too much production would be very deleterious to the host. [source] | ||||||||||||||||||||||