The Experts below are selected from a list of 10881 Experts worldwide ranked by ideXlab platform

Takahisa Furukawa - One of the best experts on this subject based on the ideXlab platform.

  • an essential role for rax homeoprotein and notch hes signaling in otx2 expression in embryonic retinal photoreceptor Cell Fate Determination
    The Journal of Neuroscience, 2011
    Co-Authors: Yuki Muranishi, Shinichi Aizawa, Koji Terada, Tatsuya Inoue, Kimiko Katoh, Toshinori Tsujii, Rikako Sanuki, Daisuke Kurokawa, Yasuhiro Tamaki, Takahisa Furukawa
    Abstract:

    The molecular mechanisms underlying Cell Fate Determination from common progenitors in the vertebrate CNS remain elusive. We previously reported that the OTX2 homeoprotein regulates retinal photoreceptor Cell Fate Determination. While Otx2 transactivation is a pivotal process for photoreceptor Cell Fate Determination, its transactivation mechanism in the retina is unknown. Here, we identified an evolutionarily conserved Otx2 enhancer of ∼500 bp, named embryonic enhancer locus for photoreceptor Otx2 transcription (EELPOT), which can recapitulate initial Otx2 expression in the embryonic mouse retina. We found that the RAX homeoprotein interacts with EELPOT to transactivate Otx2, mainly in the final Cell cycle of retinal progenitors. Conditional inactivation of Rax results in downregulation of Otx2 expression in vivo. We also showed that NOTCH–HES signaling negatively regulates EELPOT to suppress Otx2 expression. These results suggest that the integrated activity of Cell-intrinsic and -extrinsic factors on EELPOT underlies the molecular basis of photoreceptor Cell Fate Determination in the embryonic retina.

  • otx2 homeobox gene controls retinal photoreceptor Cell Fate and pineal gland development
    Nature Neuroscience, 2003
    Co-Authors: Akihiro Nishida, Akiko Furukawa, Takahisa Furukawa, Isao Matsuo, Shinichi Aizawa, Chieko Koike, Yasuo Tano
    Abstract:

    Understanding the molecular mechanisms by which distinct Cell Fate is determined during organogenesis is a central issue in development and disease. Here, using conditional gene ablation in mice, we show that the transcription factor Otx2 is essential for retinal photoreceptor Cell Fate Determination and development of the pineal gland. Otx2-deficiency converted differentiating photoreceptor Cells to amacrine-like neurons and led to a total lack of pinealocytes in the pineal gland. We also found that Otx2 transactivates the cone-rod homeobox gene Crx, which is required for terminal differentiation and maintenance of photoreceptor Cells. Furthermore, retroviral gene transfer of Otx2 steers retinal progenitor Cells toward becoming photoreceptors. Thus, Otx2 is a key regulatory gene for the Cell Fate Determination of retinal photoreceptor Cells. Our results reveal the key molecular steps required for photoreceptor Cell-Fate Determination and pinealocyte development.

Max S Wicha - One of the best experts on this subject based on the ideXlab platform.

  • role of notch signaling in Cell Fate Determination of human mammary stem progenitor Cells
    Breast Cancer Research, 2004
    Co-Authors: Gabriela Dontu, Kyle W Jackson, Erin Mcnicholas, Mari J Kawamura, Wissam M Abdallah, Max S Wicha
    Abstract:

    Introduction Notch signaling has been implicated in the regulation of Cell-Fate decisions such as self-renewal of adult stem Cells and differentiation of progenitor Cells along a particular lineage. Moreover, depending on the Cellular and developmental context, the Notch pathway acts as a regulator of Cell survival and Cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors. Methods In order to determine the role of Notch signaling in mammary Cell-Fate Determination, we have utilized a newly described in vitro system in which mammary stem/progenitor Cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists. Results Utilizing this system, we demonstrate that Notch signaling can act on mammary stem Cells to promote selfrenewal and on early progenitor Cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notchactivating DSL peptide. In addition to acting on stem Cells, Notch signaling is also able to act on multipotent progenitor Cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor Cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial Cells.

Michelle S Longworth - One of the best experts on this subject based on the ideXlab platform.

  • drosophila condensin ii subunit chromosome associated protein d3 regulates Cell Fate Determination through non Cell autonomous signaling
    Journal of Cell Science, 2016
    Co-Authors: Lindsey R Klebanow, Emanuela C Peshel, Andrew T Schuster, Kavitha Sarvepalli, Madeleine E Lemieux, Jessica J Lenoir, Adrian W Moore, Jocelyn A Mcdonald, Michelle S Longworth
    Abstract:

    The pattern of the Drosophila melanogaster adult wing is heavily influenced by the expression of proteins that dictate Cell Fate decisions between intervein and vein during development. dSRF (Blistered) expression in specific regions of the larval wing disc promotes intervein Cell Fate, whereas EGFR activity promotes vein Cell Fate. Here, we report that the chromatin-organizing protein CAP-D3 acts to dampen dSRF levels at the anterior/posterior boundary in the larval wing disc, promoting differentiation of Cells into the anterior crossvein. CAP-D3 represses KNOT expression in Cells immediately adjacent to the anterior/posterior boundary, thus blocking KNOT-mediated repression of EGFR activity and preventing Cell death. Maintenance of EGFR activity in these Cells depresses dSRF levels in the neighboring anterior crossvein progenitor Cells, allowing them to differentiate into vein Cells. These findings uncover a novel transcriptional regulatory network influencing Drosophila wing vein development, and are the first to identify a Condensin II subunit as an important regulator of EGFR activity and Cell Fate Determination in vivo.

Constance L Cepko - One of the best experts on this subject based on the ideXlab platform.

  • vertebrate neural Cell Fate Determination lessons from the retina
    Nature Reviews Neuroscience, 2001
    Co-Authors: Frederick J Livesey, Constance L Cepko
    Abstract:

    Postmitotic neurons are produced from a pool of cycling progenitors in an orderly fashion during development. Studies of Cell-Fate Determination in the vertebrate retina have uncovered several fundamental principles by which this is achieved. Most notably, a model for vertebrate Cell-Fate Determination has been proposed that combines findings on the relative roles of extrinsic and intrinsic regulators in controlling Cell-Fate choices. At the heart of the model is the proposal that progenitors pass through intrinsically determined competence states, during which they are capable of giving rise to a limited subset of Cell types under the influence of extrinsic signals.

  • the roles of intrinsic and extrinsic cues and bhlh genes in the Determination of retinal Cell Fates
    Current Opinion in Neurobiology, 1999
    Co-Authors: Constance L Cepko
    Abstract:

    A fundamental issue concerning development of the vertebrate retina is the relative contributions of extrinsic and intrinsic cues to the Determination of Cell Fate. Recent findings suggest that retinal progenitors go through a series of changes in intrinsic properties that control their competence to make different Cell types and that extrinsic cues influence the ratios of the Cell types that they produce. Recent studies of the role of the basic helix-loop-helix genes in retinal development have indicated that they can regulate competence and/or other aspects of Cell Fate Determination.

  • Cell Fate Determination in the vertebrate retina
    Proceedings of the National Academy of Sciences of the United States of America, 1996
    Co-Authors: Constance L Cepko, Christopher P Austin, Xianjie Yang, Macrene R Alexiades, Diala Ezzeddine
    Abstract:

    In the vertebrate central nervous system, the retina has been a useful model for studies of Cell Fate Determination. Recent results from studies conducted in vitro and in vivo suggest a model of retinal development in which both the progenitor Cells and the environment change over time. The model is based upon the notion that the mitotic Cells within the retina change in their response properties, or "competence", during development. These changes presage the ordered appearance of distinct Cell types during development and appear to be necessary for the production of the distinct Cell types. As the response properties of the Cells change, so too do the environmental signals that the Cells encounter. Together, intrinsic properties and extrinsic cues direct the choice of Cell Fate.

Gabriela Dontu - One of the best experts on this subject based on the ideXlab platform.

  • role of notch signaling in Cell Fate Determination of human mammary stem progenitor Cells
    Breast Cancer Research, 2004
    Co-Authors: Gabriela Dontu, Kyle W Jackson, Erin Mcnicholas, Mari J Kawamura, Wissam M Abdallah, Max S Wicha
    Abstract:

    Introduction Notch signaling has been implicated in the regulation of Cell-Fate decisions such as self-renewal of adult stem Cells and differentiation of progenitor Cells along a particular lineage. Moreover, depending on the Cellular and developmental context, the Notch pathway acts as a regulator of Cell survival and Cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors. Methods In order to determine the role of Notch signaling in mammary Cell-Fate Determination, we have utilized a newly described in vitro system in which mammary stem/progenitor Cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists. Results Utilizing this system, we demonstrate that Notch signaling can act on mammary stem Cells to promote selfrenewal and on early progenitor Cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notchactivating DSL peptide. In addition to acting on stem Cells, Notch signaling is also able to act on multipotent progenitor Cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor Cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial Cells.