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  • 1
    Language: English
    In: The European journal of neuroscience, February 2011, Vol.33(4), pp.589-98
    Description: Despite considerable progress, the mechanisms that control neural progenitor differentiation and behavior, as well as their functional integration into adult neural circuitry, are far from being understood. Given the complexity of the mammalian brain, non-mammalian models provide an excellent model to study neurogenesis, including both the cellular composition of the neurogenic microenvironment, and the factors required for precursor growth and maintenance. In particular, we chose to address the question of the control of progenitor proliferation by Sonic hedgehog (Shh) using the zebrafish dorsal mesencephalon, known as the optic tectum (OT), as a model system. Here we show that either inhibiting pharmacologically or eliminating hedgehog (Hh) signaling by using mutants that lack essential components of the Hh pathway reduces neural progenitor cell proliferation affecting neurogenesis in the OT. On the contrary, pharmacological gain-of-function experiments result in significant increase in proliferation. Importantly, Shh-dependent function controls neural progenitor cell behavior as sox2-positive cell populations were lost in the OT in the absence of Hh signaling, as evidenced in slow-muscle-omitted (smu) mutants and with timed cyclopamine inhibition. Expressions of essential components of the Hh pathway reveal for the first time a late dorsal expression in the embryonic OT. Our observations argue strongly for a role of Shh in neural progenitor biology in the OT and provide comparative data to our current understanding of progenitor/stem cell mechanisms that place Shh as a key niche factor in the dorsal brain.
    Keywords: Tectum Mesencephali ; Zebrafish ; Cell Division -- Physiology ; Hedgehog Proteins -- Metabolism ; Neural Stem Cells -- Physiology ; Signal Transduction -- Physiology ; Zebrafish Proteins -- Metabolism
    ISSN: 0953816X
    E-ISSN: 1460-9568
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  • 2
    Language: English
    In: Cancer Research, 04/01/2016, Vol.76(7 Supplement), pp.B50-B50
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 3
    In: International Journal of Cancer, 01 January 2014, Vol.134(1), pp.21-31
    Description: The canonical Sonic Hedgehog (Shh)/Gli pathway plays multiples roles during central nervous system (CNS) development. To elucidate the molecular repertoire of Shh mediators, we have recently described novel transcriptional targets in response to Shh pathway modulation. Among them, we were able to identify Neogenin1 (Neo1), a death dependence receptor, as a new direct Shh downstream regulator in neural precursor proliferation. As appropriate Shh signaling is required for cerebellar growth and alterations cause Shh‐driven medulloblastoma (MB), here we have addressed the role of the Shh/Neogenin1 interaction in the context of cerebellar development and cancer. We demonstrate that the Shh pathway regulates Neogenin1 expression in mouse models that recapitulate the Shh MB subtype. We show that the canonical Shh pathway directly regulates the gene acting through an upstream sequence in its promoter both and in granule neuron precursor cells. We also identified and characterized a functional Gli‐binding site in the first intron of the human gene. Gene expression profiling of more than 300 MB shows that is indeed upregulated in SHH tumors compared to the other MB subgroups. Finally, we provide evidence that NEO1 is necessary for cell cycle progression in a human MB cell line, because a loss of function of arrests cells in the G2/M phase. Taken together, these results highlight Neogenin1 as a novel downstream effector of the Shh pathway in MB and a possible therapeutic target. What's new? Abnormal activation of the canonical Sonic Hedgehog (Shh)/Gli pathway has been associated with up to 30% of the human cases of medulloblastoma, which represents the most common malignant primary brain tumor in children. A greater knowledge of the cellular response to Shh pathway activation in the cerebellum is critical for both understanding disease formation and developing new treatments. In this study, the authors identified Neogenin‐1 as a novel downstream effector of the Shh pathway that mediates proliferation in both cultured cerebellar progenitors and shh‐driven medulloblastoma. The data suggest that targeting Neogenin‐1 could offer a promising alternative to current anti‐medulloblastoma therapies.
    Keywords: Medulloblastoma ; Sonic Hedgehog ; Neogenin 1 ; Gli ; Cancer
    ISSN: 0020-7136
    E-ISSN: 1097-0215
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  • 4
    Language: English
    In: Genetics, May 2014, Vol.197(1), pp.175-92
    Description: Insulin-producing cells (IPCs) in the Drosophila brain produce and release insulin-like peptides (ILPs) to the hemolymph. ILPs are crucial for growth and regulation of metabolic activity in flies, functions analogous to those of mammalian insulin and insulin-like growth factors (IGFs). To identify components functioning in IPCs to control ILP production, we employed genomic and candidate gene approaches. We used laser microdissection and messenger RNA sequencing to characterize the transcriptome of larval IPCs. IPCs highly express many genes homologous to genes active in insulin-producing β-cells of the mammalian pancreas. The genes in common encode ILPs and proteins that control insulin metabolism, storage, secretion, β-cell proliferation, and some not previously linked to insulin production or β-cell function. Among these novelties is unc-104, a kinesin 3 family gene, which is more highly expressed in IPCs compared to most other neurons. Knockdown of unc-104 in IPCs impaired ILP secretion and reduced peripheral insulin signaling. Unc-104 appears to transport ILPs along axons. As a complementary approach, we tested dominant-negative Rab genes to find Rab proteins required in IPCs for ILP production or secretion. Rab1 was identified as crucial for ILP trafficking in IPCs. Inhibition of Rab1 in IPCs increased circulating sugar levels, delayed development, and lowered weight and body size. Immunofluorescence labeling of Rab1 showed its tight association with ILP2 in the Golgi of IPCs. Unc-104 and Rab1 join other proteins required for ILP transport in IPCs.
    Keywords: Drosophila ; Er ; Golgi ; RNA-Seq ; Rab1 ; Unc-104 ; Insulin ; Kinesin ; Laser Microdissection ; Pancreas ; Transport ; Gene Expression Profiling ; Drosophila Melanogaster -- Cytology ; Insulin -- Metabolism ; Insulin-Secreting Cells -- Metabolism
    ISSN: 00166731
    E-ISSN: 1943-2631
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  • 5
    Language: Portuguese
    In: Biological Research, January 2012, Vol.45(3), pp.223-230
    Description: The Sonic Hegdehog/GLI (SHH/GLI) pathway has been extensively studied for its role in developmental and cancer biology. During early embryonic development the SHH pathway is involved mainly in pattern formation, while in latter stages its function in stem cell and progenitor proliferation becomes increasingly relevant. During postnatal development and in adult tissues, SHH/GLI promotes cell homeostasis by actively regulating gene transcription, recapitulating the function observed during normal tissue growth. In this review, we will briefly discuss the fundamental importance of SHH/GLI in tumor growth and cancer evolution and we will then provide insights into a possible novel mechanism of SHH action in cancer through autophagy modulation in cancer stem cells. Autophagy is a homeostatic mechanism that when disrupted can promote and accelerate tumor progression in both cancer cells and the stroma that harbors tumorigenesis. Understanding possible new targets for SHH signaling and its contribution to cancer through modulation of autophagy might provide better strategies in order to design combined treatments and perform clinical trials.
    Keywords: Biology ; Cancer Stem Cells ; Sonic Hedgehog ; Cell Survival ; Autophagy ; Neuroblastoma ; Cancer Therapy ; Biology
    ISSN: 0716-9760
    E-ISSN: 0717-6287
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  • 6
    Language: English
    In: Developmental Biology, 15 July 2009, Vol.331(2), pp.439-439
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.05.192 Byline: Claudio R. Cortes, Luis A. Milla, Veronica Palma Author Affiliation: Center for Genomics of the Cell, Department Biol. Sc, University of Chile, Santiago, Chile
    Keywords: Biology ; Zoology
    ISSN: 0012-1606
    E-ISSN: 1095-564X
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  • 7
    In: Industrial Data, 03/31/2014, Vol.3(1), p.28
    Description: el avance de la tecnología ha hecho imprescindible el uso de la computadora en la industria como una herrameinta de control. su aplicaci{on es cada vez más intensiva, y por tal motivo este artículo señala el desarrollo histórico de su aplicación, y las posibilidades que se tendrá en el futuro.
    Keywords: Engineering;
    ISSN: 1560-9146
    E-ISSN: 1810-9993
    Source: CrossRef
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  • 8
    In: Industrial Data, 04/02/2014, Vol.3(2), p.11
    Description: los estudios, proyectos y trabajos de investigación requieren de modelos matemáticos que optimicen la trayectoria de la curva que se obtenga de una muestra histórica o de un conjunto de datos obtenidos en el terreno o en el laboratorio a fin de que se adecúen sus variables a las mismas.
    Keywords: Engineering;
    ISSN: 1560-9146
    E-ISSN: 1810-9993
    Source: CrossRef
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  • 9
    In: Industrial Data, 04/04/2014, Vol.5(2), p.78
    Description: 〈span style="font-family: Verdana; font-size: x-small;"〉La energía convencional y no convencional constituye una necesidad en el mundo moderno del cual el ser humano no puede prescindir, sin embargo existen varios problemas, tales como; la escasez, el costo, el agotamiento, la captación, la contaminación, por tal motivo se debe hacer un seguimiento de la evolución de cada uno de estos tipos de energía donde no sólo priorice su costo de instalación ni el precio por KHH, sino la oportunidad de tener la energía para un determinado fin.〈/span〉
    Keywords: Engineering;
    ISSN: 1560-9146
    E-ISSN: 1810-9993
    Source: CrossRef
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  • 10
    In: Industrial Data, 03/29/2014, Vol.2(2), p.59
    Description: 〈span style="font-family: Verdana; font-size: x-small;"〉El presente artículo nos reseña el desarrollo de la cibernética y su impacto en la Ingeniería Industrial.〈/span〉
    Keywords: Engineering;
    ISSN: 1560-9146
    E-ISSN: 1810-9993
    Source: CrossRef
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