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  1. Article ; Online: An autoregulatory cell cycle timer integrates growth and specification in chick wing digit development.

    Pickering, Joseph / Chinnaiya, Kavitha / Towers, Matthew

    eLife

    2019  Volume 8

    Abstract: A fundamental question is how proliferation and growth are timed during embryogenesis. Although it has been suggested that the cell cycle could be a timer, the underlying mechanisms remain elusive. Here we describe a cell cycle timer that operates ... ...

    Abstract A fundamental question is how proliferation and growth are timed during embryogenesis. Although it has been suggested that the cell cycle could be a timer, the underlying mechanisms remain elusive. Here we describe a cell cycle timer that operates in
    MeSH term(s) Animals ; Bone Morphogenetic Protein 2/metabolism ; Cell Cycle ; Cell Proliferation ; Chick Embryo ; Cyclin D/metabolism ; Gene Expression Regulation, Developmental ; Hedgehog Proteins/metabolism ; Signal Transduction ; Wings, Animal/embryology
    Chemical Substances Bone Morphogenetic Protein 2 ; Cyclin D ; Hedgehog Proteins
    Language English
    Publishing date 2019-09-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.47625
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Inhibition of Shh signalling in the chick wing gives insights into digit patterning and evolution.

    Pickering, Joseph / Towers, Matthew

    Development (Cambridge, England)

    2016  Volume 143, Issue 19, Page(s) 3514–3521

    Abstract: In an influential model of pattern formation, a gradient of Sonic hedgehog (Shh) signalling in the chick wing bud specifies cells with three antero-posterior positional values, which give rise to three morphologically different digits by a self- ... ...

    Abstract In an influential model of pattern formation, a gradient of Sonic hedgehog (Shh) signalling in the chick wing bud specifies cells with three antero-posterior positional values, which give rise to three morphologically different digits by a self-organizing mechanism with Turing-like properties. However, as four of the five digits of the mouse limb are morphologically similar in terms of phalangeal pattern, it has been suggested that self-organization alone could be sufficient. Here, we show that inhibition of Shh signalling at a specific stage of chick wing development results in a pattern of four digits, three of which can have the same number of phalanges. These patterning changes are dependent on a posterior extension of the apical ectodermal ridge, and this also allows the additional digit to arise from the Shh-producing cells of the polarizing region - an ability lost in ancestral theropod dinosaurs. Our analyses reveal that, if the specification of antero-posterior positional values is curtailed, self-organization can then produce several digits with the same number of phalanges. We present a model that may give important insights into how the number of digits and phalanges has diverged during the evolution of avian and mammalian limbs.
    MeSH term(s) Animals ; Apoptosis/genetics ; Apoptosis/physiology ; Biological Evolution ; Body Patterning/genetics ; Body Patterning/physiology ; Chick Embryo ; Embryo, Mammalian/metabolism ; Flow Cytometry ; Gene Expression Regulation, Developmental/genetics ; Gene Expression Regulation, Developmental/physiology ; Hedgehog Proteins/genetics ; Hedgehog Proteins/metabolism ; In Situ Hybridization ; Mice ; Morphogenesis/genetics ; Morphogenesis/physiology ; Signal Transduction/genetics ; Signal Transduction/physiology ; Wings, Animal/embryology ; Wings, Animal/metabolism
    Chemical Substances Hedgehog Proteins
    Language English
    Publishing date 2016-10-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 90607-4
    ISSN 1477-9129 ; 0950-1991
    ISSN (online) 1477-9129
    ISSN 0950-1991
    DOI 10.1242/dev.137398
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning.

    Sedas Perez, Sofia / McQueen, Caitlin / Stainton, Holly / Pickering, Joseph / Chinnaiya, Kavitha / Saiz-Lopez, Patricia / Placzek, Marysia / Ros, Maria A / Towers, Matthew

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 5841

    Abstract: Complex signalling between the apical ectodermal ridge (AER - a thickening of the distal epithelium) and the mesoderm controls limb patterning along the proximo-distal axis (humerus to digits). However, the essential in vivo requirement for AER-Fgf ... ...

    Abstract Complex signalling between the apical ectodermal ridge (AER - a thickening of the distal epithelium) and the mesoderm controls limb patterning along the proximo-distal axis (humerus to digits). However, the essential in vivo requirement for AER-Fgf signalling makes it difficult to understand the exact roles that it fulfils. To overcome this barrier, we developed an amenable ex vivo chick wing tissue explant system that faithfully replicates in vivo parameters. Using inhibition experiments and RNA-sequencing, we identify a transient role for Fgfs in triggering the distal patterning phase. Fgfs are then dispensable for the maintenance of an intrinsic mesodermal transcriptome, which controls proliferation/differentiation timing and the duration of patterning. We also uncover additional roles for Fgf signalling in maintaining AER-related gene expression and in suppressing myogenesis. We describe a simple logic for limb patterning duration, which is potentially applicable to other systems, including the main body axis.
    MeSH term(s) Animals ; Chickens ; Epithelium ; Extremities ; Fibroblast Growth Factors/genetics ; Mesoderm
    Chemical Substances Fibroblast Growth Factors (62031-54-3)
    Language English
    Publishing date 2023-09-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-41457-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Transcriptional changes in chick wing bud polarization induced by retinoic acid.

    Pickering, Joseph / Wali, Neha / Towers, Matthew

    Developmental dynamics : an official publication of the American Association of Anatomists

    2017  Volume 246, Issue 9, Page(s) 682–690

    Abstract: Background: Retinoic acid is implicated in the induction of the gene encoding Sonic hedgehog (Shh) that specifies anteroposterior positional values and promotes growth of the developing limb bud. However, because retinoic acid is involved in limb ... ...

    Abstract Background: Retinoic acid is implicated in the induction of the gene encoding Sonic hedgehog (Shh) that specifies anteroposterior positional values and promotes growth of the developing limb bud. However, because retinoic acid is involved in limb initiation, it has been difficult to determine if it could have additional roles in anteroposterior patterning. To investigate this, we implanted retinoic acid-soaked beads to the anterior margin of the chick wing bud and performed microarray analyses prior to onset of Shh expression.
    Results: Retinoic acid up-regulates expression of Hoxd11-13 that encode transcription factors implicated in inducing Shh transcription and that are involved in digit development. In our assay, retinoic acid induces Shh transcription and, consequently, a new pattern of digits at a much later stage than anticipated. Retinoic acid represses many anteriorly expressed genes, including Bmp4, Lhx9, Msx2, and Alx4. We provide evidence that retinoic acid influences transcription via induction of dHAND and inhibition of Gli3 to establish a new anteroposterior pre-pattern. We show that transient exposure to retinoic acid can suppress distal development and expedite cells to transcriptionally respond to Shh.
    Conclusions: Our findings reveal how retinoic acid and Shh signaling could cooperate in anteroposterior patterning of the limb. Developmental Dynamics 246:682-690, 2017. © 2017 Wiley Periodicals, Inc.
    MeSH term(s) Animals ; Body Patterning/physiology ; Gene Expression Regulation, Developmental/genetics ; Gene Expression Regulation, Developmental/physiology ; Hedgehog Proteins/metabolism ; Limb Buds/embryology ; Limb Buds/metabolism ; Tretinoin/pharmacology ; Wings, Animal/embryology ; Wings, Animal/metabolism
    Chemical Substances Hedgehog Proteins ; Tretinoin (5688UTC01R)
    Language English
    Publishing date 2017-07-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1102541-4
    ISSN 1097-0177 ; 1058-8388
    ISSN (online) 1097-0177
    ISSN 1058-8388
    DOI 10.1002/dvdy.24543
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Hedgehog signalling acts upstream of Laminin alpha1 transcription in the zebrafish paraxial mesoderm.

    Pickering, Joseph / Cunliffe, Vincent T / Van Eeden, Freek / Borycki, Anne-Gaëlle

    Matrix biology : journal of the International Society for Matrix Biology

    2017  Volume 62, Page(s) 58–74

    Abstract: Laminin-111 (α1β1γ1) is a member of the Laminin family of extra-cellular matrix proteins that comprises 16 members, components of basement membranes. Laminin-111, one of the first Laminin proteins synthesised during embryogenesis, is required for ... ...

    Abstract Laminin-111 (α1β1γ1) is a member of the Laminin family of extra-cellular matrix proteins that comprises 16 members, components of basement membranes. Laminin-111, one of the first Laminin proteins synthesised during embryogenesis, is required for basement membrane deposition and has essential roles in tissue morphogenesis and patterning. Yet, the mechanisms controlling Laminin-111 expression are poorly understood. We generated a zebrafish transgenic reporter line that reproduces faithfully the expression pattern of lama1, the gene encoding Laminin α1, and we used this reporter line to investigate lama1 transcriptional regulation. Our findings established that lama1 expression is controlled by intronic enhancers, including an enhancer directing expression in the paraxial mesoderm, anterior spinal cord and hindbrain, located in intron 1. We show that Hedgehog signalling is necessary and sufficient for lama1 transcription in the paraxial mesoderm and identify putative Gli/Zic binding sites that may mediate this control. These findings uncover a conserved role for Hedgehog signalling in the control of basement membrane assembly via its transcriptional regulation of lama1, and provide a mechanism to coordinate muscle cell fate specification in the zebrafish embryo.
    Language English
    Publishing date 2017-10
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1183793-7
    ISSN 1569-1802 ; 0945-053X
    ISSN (online) 1569-1802
    ISSN 0945-053X
    DOI 10.1016/j.matbio.2016.11.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: An intrinsic cell cycle timer terminates limb bud outgrowth.

    Pickering, Joseph / Rich, Constance A / Stainton, Holly / Aceituno, Cristina / Chinnaiya, Kavitha / Saiz-Lopez, Patricia / Ros, Marian A / Towers, Matthew

    eLife

    2018  Volume 7

    Abstract: The longstanding view of how proliferative outgrowth terminates following the patterning phase of limb development involves the breakdown of reciprocal extrinsic signalling between the distal mesenchyme and the overlying epithelium (e-m signalling). ... ...

    Abstract The longstanding view of how proliferative outgrowth terminates following the patterning phase of limb development involves the breakdown of reciprocal extrinsic signalling between the distal mesenchyme and the overlying epithelium (e-m signalling). However, by grafting distal mesenchyme cells from late stage chick wing buds to the epithelial environment of younger wing buds, we show that this mechanism is not required. RNA sequencing reveals that distal mesenchyme cells complete proliferative outgrowth by an intrinsic cell cycle timer in the presence of e-m signalling. In this process, e-m signalling is required permissively to allow the intrinsic cell cycle timer to run its course. We provide evidence that a temporal switch from BMP antagonism to BMP signalling controls the intrinsic cell cycle timer during limb outgrowth. Our findings have general implications for other patterning systems in which extrinsic signals and intrinsic timers are integrated.
    MeSH term(s) Animals ; Cell Cycle/genetics ; Cell Proliferation/genetics ; Chickens ; Epithelium/growth & development ; Extremities/growth & development ; Gene Expression Regulation, Developmental ; Limb Buds/growth & development ; Limb Buds/metabolism ; Mesoderm/growth & development ; Organogenesis/genetics ; Sequence Analysis, RNA ; Signal Transduction/genetics
    Language English
    Publishing date 2018-09-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.37429
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Book ; Online: Inquiries of an emigrant

    Pickering, Joseph

    being the narrative of an English farmer from the year 1824 to 1830, with the author's additions, to March 1832

    1832  

    Author's details by Joseph Pickering
    Keywords Canada ; Great Britain ; Ontario ; United States
    Language English
    Size Online-Ressource
    Edition 4th ed
    Publisher E. Wilson
    Publishing place London
    Document type Book ; Online
    Note Goldsmiths'-Kress no. 27291 ; OCLC, 18004112 ; Reproduction of original from Goldsmiths' Library, University of London
    Database Former special subject collection: coastal and deep sea fishing

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  8. Book ; Online: Emigration, or no emigration

    Pickering, Joseph

    being the narrative of the author, (an English farmer), from the year 1824 to 1830, during which time he traversed the United States of America, and the British province of Canada, with a view to settle as an emigrant

    1830  

    Author's details by Joseph Pickering
    Keywords Ontario ; United States
    Language English
    Size Online-Ressource, 18 cm
    Publisher Printed for the author, published by Longman, Rees, Orme, Brown, and Green
    Publishing place London
    Document type Book ; Online
    Note Goldsmiths'-Kress no. 26111 ; OCLC, 18278631 ; Reproduction of original from Goldsmiths' Library, University of London
    Database Former special subject collection: coastal and deep sea fishing

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