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  1. Article ; Online: Kathryn Anderson (1952-2020).

    Huangfu, Danwei / García-García, María J / Eggenschwiler, Jonathan

    Developmental cell

    2021  Volume 56, Issue 3, Page(s) 257–259

    Language English
    Publishing date 2021-03-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2021.01.009
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    Zs.A 5742: Show issues Location:
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  2. Article ; Online: Hedgehog signaling and the cilium: in the zone.

    Eggenschwiler, Jonathan

    Developmental cell

    2012  Volume 23, Issue 4, Page(s) 677–678

    Abstract: Hedgehog signaling is transduced at the primary cilium, but the precise mechanisms underlying this action are not clear. In this issue of Developmental Cell, Dorn and colleagues (2012) describe a novel mechanism for control of Hedgehog signaling by Evc ... ...

    Abstract Hedgehog signaling is transduced at the primary cilium, but the precise mechanisms underlying this action are not clear. In this issue of Developmental Cell, Dorn and colleagues (2012) describe a novel mechanism for control of Hedgehog signaling by Evc proteins within the primary cilium.
    Language English
    Publishing date 2012-10-16
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2012.10.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Hedgehog Signaling and the Cilium: in the Zone

    Eggenschwiler, Jonathan

    Developmental cell. 2012 Oct. 16, v. 23, no. 4

    2012  

    Abstract: Hedgehog signaling is transduced at the primary cilium, but the precise mechanisms underlying this action are not clear. In this issue of Developmental Cell, Dorn and colleagues (2012) describe a novel mechanism for control of Hedgehog signaling by Evc ... ...

    Abstract Hedgehog signaling is transduced at the primary cilium, but the precise mechanisms underlying this action are not clear. In this issue of Developmental Cell, Dorn and colleagues (2012) describe a novel mechanism for control of Hedgehog signaling by Evc proteins within the primary cilium.
    Keywords cilia ; proteins ; signal transduction
    Language English
    Dates of publication 2012-1016
    Size p. 677-678.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2012.10.001
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  4. Article ; Online: Identifying essential genes in mouse development via an ENU-based forward genetic approach.

    Liu, Aimin / Eggenschwiler, Jonathan

    Methods in molecular biology (Clifton, N.J.)

    2014  Volume 1092, Page(s) 95–118

    Abstract: The completion of the human and mouse genome projects at the beginning of the past decade represented a very important step forward in our pursuit of a comprehensive understanding of the genetic control of mammalian development. Nevertheless, genetic ... ...

    Abstract The completion of the human and mouse genome projects at the beginning of the past decade represented a very important step forward in our pursuit of a comprehensive understanding of the genetic control of mammalian development. Nevertheless, genetic analyses of mutant phenotypes are still needed to understand the function of individual genes. The genotype-based approaches, including gene-trapping and gene-targeting, promise a mutant embryonic stem (ES) cell resource for all the genes in mouse genome; however, the phenotypic consequences of these mutations will not be addressed until mutant mice are derived from these ES cells, which is not trivial. An efficient and non-biased, N-ethyl-N-nitrosourea (ENU)-based forward genetic approach in mouse provides a unique tool for the identification of genes essential for development and adult physiology. We have had great success in identifying genes essential for morphogenesis and early patterning of mouse via this approach. Combined with complete genome information and numerous genetic resources available, ENU-based mutagenesis has become a powerful tool in deciphering gene functions.
    MeSH term(s) Animals ; Embryo, Mammalian ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Ethylnitrosourea/toxicity ; Genes, Essential ; Genome ; Humans ; Mice ; Molecular Biology/methods ; Morphogenesis
    Chemical Substances Ethylnitrosourea (P8M1T4190R)
    Language English
    Publishing date 2014
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-60327-292-6_7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Proper ciliary assembly is critical for restricting Hedgehog signaling during early eye development in mice.

    Burnett, Jacob B / Lupu, Floria I / Eggenschwiler, Jonathan T

    Developmental biology

    2017  Volume 430, Issue 1, Page(s) 32–40

    Abstract: Patterning of the vertebrate eye into optic stalk, retinal pigment epithelium (RPE) and neural retina (NR) territories relies on a number of signaling pathways, but how these signals are interpreted by optic progenitors is not well understood. The ... ...

    Abstract Patterning of the vertebrate eye into optic stalk, retinal pigment epithelium (RPE) and neural retina (NR) territories relies on a number of signaling pathways, but how these signals are interpreted by optic progenitors is not well understood. The primary cilium is a microtubule-based organelle that is essential for Hedgehog (Hh) signaling, but it has also been implicated in the regulation of other signaling pathways. Here, we show that the optic primordium is ciliated during early eye development and that ciliogenesis is essential for proper patterning and morphogenesis of the mouse eye. Ift172 mutants fail to generate primary cilia and exhibit patterning defects that resemble those of Gli3 mutants, suggesting that cilia are required to restrict Hh activity during eye formation. Ift122 mutants, which produce cilia with abnormal morphology, generate optic vesicles that fail to invaginate to produce the optic cup. These mutants also lack formation of the lens, RPE and NR. Such phenotypic features are accompanied by strong, ectopic Hh pathway activity, evidenced by altered gene expression patterns. Removal of GLI2 from Ift122 mutants rescued several aspects of optic cup and lens morphogenesis as well as RPE and NR specification. Collectively, our data suggest that proper assembly of primary cilia is critical for restricting the Hedgehog pathway during eye formation in the mouse.
    MeSH term(s) Animals ; Body Patterning ; Cilia/metabolism ; Eye/embryology ; Eye/metabolism ; Hedgehog Proteins/metabolism ; Intracellular Signaling Peptides and Proteins/metabolism ; Kruppel-Like Transcription Factors/metabolism ; Lens, Crystalline/cytology ; Lens, Crystalline/metabolism ; Mice ; Models, Biological ; Morphogenesis ; Mutation/genetics ; Signal Transduction ; Stem Cells/cytology ; Stem Cells/metabolism ; Zinc Finger Protein Gli2
    Chemical Substances Gli2 protein, mouse ; Hedgehog Proteins ; Ift122 protein, mouse ; Ift172 protein, mouse ; Intracellular Signaling Peptides and Proteins ; Kruppel-Like Transcription Factors ; Zinc Finger Protein Gli2
    Language English
    Publishing date 2017-08-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1114-9
    ISSN 1095-564X ; 0012-1606
    ISSN (online) 1095-564X
    ISSN 0012-1606
    DOI 10.1016/j.ydbio.2017.07.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Cell cycle-related kinase regulates mammalian eye development through positive and negative regulation of the Hedgehog pathway.

    Lupu, Floria I / Burnett, Jacob B / Eggenschwiler, Jonathan T

    Developmental biology

    2017  Volume 434, Issue 1, Page(s) 24–35

    Abstract: Cell cycle-related kinase (CCRK) is a conserved regulator of ciliogenesis whose loss in mice leads to a wide range of developmental defects, including exencephaly, preaxial polydactyly, skeletal abnormalities, and microphthalmia. Here, we investigate the ...

    Abstract Cell cycle-related kinase (CCRK) is a conserved regulator of ciliogenesis whose loss in mice leads to a wide range of developmental defects, including exencephaly, preaxial polydactyly, skeletal abnormalities, and microphthalmia. Here, we investigate the role of CCRK in mouse eye development. Ccrk mutants show dramatic patterning defects, with an expansion of the optic stalk domain into the optic cup, as well as an expansion of the retinal pigment epithelium (RPE) into neural retina (NR) territory. In addition, Ccrk mutants display a shortened optic stalk. These defects are associated with bimodal changes in Hedgehog (Hh) pathway activity within the eye, including the loss of proximal, high level responses but a gain in distal, low level responses. We simultaneously removed the Hh activator GLI2 in Ccrk mutants (Ccrk-/-;Gli2-/-), which resulted in rescue of optic cup patterning and exacerbation of optic stalk length defects. Next, we disrupted the Hh pathway antagonist GLI3 in mutants lacking CCRK (Ccrk-/-;Gli3-/-), which lead to even greater expansion of the RPE markers into the NR domain and a complete loss of NR specification within the optic cup. These results indicate that CCRK functions in eye development by both positively and negatively regulating the Hh pathway, and they reveal distinct requirements for Hh signaling in patterning and morphogenesis of the eyes.
    MeSH term(s) Animals ; Cyclin-Dependent Kinases/genetics ; Cyclin-Dependent Kinases/metabolism ; Embryo, Mammalian/cytology ; Embryo, Mammalian/embryology ; Eye/cytology ; Eye/embryology ; Female ; Hedgehog Proteins/genetics ; Hedgehog Proteins/metabolism ; Male ; Mice ; Mice, Mutant Strains ; Organogenesis/physiology ; Signal Transduction/physiology ; Zinc Finger Protein Gli2/genetics ; Zinc Finger Protein Gli2/metabolism
    Chemical Substances Gli2 protein, mouse ; Hedgehog Proteins ; Zinc Finger Protein Gli2 ; Cyclin-Dependent Kinases (EC 2.7.11.22) ; cyclin-dependent kinase-activating kinase (EC 2.7.11.22)
    Language English
    Publishing date 2017-11-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1114-9
    ISSN 1095-564X ; 0012-1606
    ISSN (online) 1095-564X
    ISSN 0012-1606
    DOI 10.1016/j.ydbio.2017.10.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Cell cycle-related kinase regulates mammalian eye development through positive and negative regulation of the Hedgehog pathway

    Lupu, Floria I / Burnett, Jacob B / Eggenschwiler, Jonathan T

    Developmental biology. 2017,

    2017  

    Abstract: Cell cycle-related kinase (CCRK) is a conserved regulator of ciliogenesis whose loss in mice leads to a wide range of developmental defects, including exencephaly, preaxial polydactyly, skeletal abnormalities, and microphthalmia. Here, we investigate the ...

    Abstract Cell cycle-related kinase (CCRK) is a conserved regulator of ciliogenesis whose loss in mice leads to a wide range of developmental defects, including exencephaly, preaxial polydactyly, skeletal abnormalities, and microphthalmia. Here, we investigate the role of CCRK in mouse eye development. Ccrk mutants show dramatic patterning defects, with an expansion of the optic stalk domain into the optic cup, as well as an expansion of the retinal pigment epithelium (RPE) into neural retina (NR) territory. In addition, Ccrk mutants display a shortened optic stalk. These defects are associated with bimodal changes in Hedgehog (Hh) pathway activity within the eye, including the loss of proximal, high level responses but a gain in distal, low level responses. We simultaneously removed the Hh activator GLI2 in Ccrk mutants (Ccrk-/-;Gli2-/-), which resulted in rescue of optic cup patterning and exacerbation of optic stalk length defects. Next, we disrupted the Hh pathway antagonist GLI3 in mutants lacking CCRK (Ccrk-/-;Gli3-/-) which lead to even greater expansion of the RPE markers into the NR domain and a complete loss of NR specification within the optic cup. These results indicate that CCRK functions in eye development by both positively and negatively regulating the Hh pathway, and they reveal distinct requirements for Hh signaling in patterning and morphogenesis of the eyes.
    Keywords antagonists ; epithelium ; mice ; morphogenesis ; mutants ; retina
    Language English
    Publishing place Elsevier Inc.
    Document type Article
    Note Pre-press version
    ZDB-ID 1114-9
    ISSN 1095-564X ; 0012-1606
    ISSN (online) 1095-564X
    ISSN 0012-1606
    DOI 10.1016/j.ydbio.2017.10.022
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  8. Article: Proper ciliary assembly is critical for restricting Hedgehog signaling during early eye development in mice

    Burnett, Jacob B / Lupu, Floria I / Eggenschwiler, Jonathan T

    Developmental biology. 2017,

    2017  

    Abstract: Patterning of the vertebrate eye into optic stalk, retinal pigment epithelium (RPE) and neural retina (NR) territories relies on a number of signaling pathways, but how these signals are interpreted by optic progenitors is not well understood. The ... ...

    Abstract Patterning of the vertebrate eye into optic stalk, retinal pigment epithelium (RPE) and neural retina (NR) territories relies on a number of signaling pathways, but how these signals are interpreted by optic progenitors is not well understood. The primary cilium is a microtubule-based organelle that is essential for Hedgehog (Hh) signaling, but it has also been implicated in the regulation of other signaling pathways. Here, we show that the optic primordium is ciliated during early eye development and that ciliogenesis is essential for proper patterning and morphogenesis of the mouse eye. Ift172 mutants fail to generate primary cilia and exhibit patterning defects that resemble those of Gli3 mutants, suggesting that cilia are required to restrict Hh activity during eye formation. Ift122 mutants, which produce cilia with abnormal morphology, generate optic vesicles that fail to invaginate to produce the optic cup. These mutants also lack formation of the lens, RPE and NR. Such phenotypic features are accompanied by strong, ectopic Hh pathway activity, evidenced by altered gene expression patterns. Removal of GLI2 from Ift122 mutants rescued several aspects of optic cup and lens morphogenesis as well as RPE and NR specification. Collectively, our data suggest that proper assembly of primary cilia is critical for restricting the Hedgehog pathway during eye formation in the mouse.
    Keywords cilia ; epithelium ; gene expression regulation ; mice ; morphogenesis ; mutants ; phenotype ; retina ; signal transduction
    Language English
    Publishing place Elsevier Inc.
    Document type Article
    Note Pre-press version
    ZDB-ID 1114-9
    ISSN 1095-564X ; 0012-1606
    ISSN (online) 1095-564X
    ISSN 0012-1606
    DOI 10.1016/j.ydbio.2017.07.012
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Cilia and developmental signaling.

    Eggenschwiler, Jonathan T / Anderson, Kathryn V

    Annual review of cell and developmental biology

    2007  Volume 23, Page(s) 345–373

    Abstract: Recent studies have revealed unexpected connections between the mammalian Hedgehog (Hh) signal transduction pathway and the primary cilium, a microtubule-based organelle that protrudes from the surface of most vertebrate cells. Intraflagellar transport ... ...

    Abstract Recent studies have revealed unexpected connections between the mammalian Hedgehog (Hh) signal transduction pathway and the primary cilium, a microtubule-based organelle that protrudes from the surface of most vertebrate cells. Intraflagellar transport proteins, which are required for the construction of cilia, are essential for all responses to mammalian Hh proteins, and proteins required for Hh signal transduction are enriched in primary cilia. The phenotypes of different mouse mutants that affect ciliary proteins suggest that cilia may act as processive machines that organize sequential steps in the Hh signal transduction pathway. Cilia on vertebrate cells are likely to be important in additional developmental signaling pathways and are required for PDGF receptor alpha signaling in cultured fibroblasts. Cilia are not essential for either canonical or noncanonical Wnt signaling, although cell-type-specific modulation of cilia components may link cilia and Wnt signaling in some tissues. Because ciliogenesis in invertebrates is limited to a very small number of specialized cell types, the role of cilia in developmental signaling pathways is likely a uniquely vertebrate phenomenon.
    MeSH term(s) Animals ; Body Patterning ; Cilia/physiology ; Genetic Diseases, Inborn/metabolism ; Hedgehog Proteins/metabolism ; Humans ; Mice ; Neural Tube/growth & development ; Protein Transport/genetics ; Signal Transduction
    Chemical Substances Hedgehog Proteins
    Language English
    Publishing date 2007
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1293750-2
    ISSN 1530-8995 ; 1081-0706
    ISSN (online) 1530-8995
    ISSN 1081-0706
    DOI 10.1146/annurev.cellbio.23.090506.123249
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  10. Article ; Online: MiCASA is a new method for quantifying cellular organization.

    Sornborger, Andrew / Li, Jie / Timmons, Cullen / Lupu, Floria / Eggenschwiler, Jonathan / Takahama, Yousuke / Manley, Nancy R

    Nature communications

    2017  Volume 8, Page(s) 15619

    Abstract: While many tools exist for identifying and quantifying individual cell types, few methods are available to assess the relationships between cell types in organs and tissues and how these relationships change during aging or disease states. We present a ... ...

    Abstract While many tools exist for identifying and quantifying individual cell types, few methods are available to assess the relationships between cell types in organs and tissues and how these relationships change during aging or disease states. We present a quantitative method for evaluating cellular organization, using the mouse thymus as a test organ. The thymus is the primary lymphoid organ responsible for generating T cells in vertebrates, and its proper structure and organization is essential for optimal function. Our method, Multitaper Circularly Averaged Spectral Analysis (MiCASA), identifies differences in the tissue-level organization with high sensitivity, including defining a novel type of phenotype by measuring variability as a specific parameter. MiCASA provides a novel and easily implemented quantitative tool for assessing cellular organization.
    MeSH term(s) Animals ; CD11c Antigen/metabolism ; Diagnosis, Computer-Assisted/methods ; Genotype ; Image Processing, Computer-Assisted/methods ; Lymphoid Tissue/diagnostic imaging ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Phenotype ; Spectrophotometry/methods ; Spinal Cord/diagnostic imaging ; Spinal Cord/embryology ; T-Lymphocytes/cytology ; Thymus Gland/diagnostic imaging
    Chemical Substances CD11c Antigen
    Language English
    Publishing date 2017-05-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2041-1723
    ISSN (online) 2041-1723
    DOI 10.1038/ncomms15619
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