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  • 1
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    Online Resource
    Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus
    The Company of Biologists ; 2015
    In:  Development Vol. 142, No. 19 ( 2015-10-01), p. 3416-3428
    Details
    In: Development, The Company of Biologists, Vol. 142, No. 19 ( 2015-10-01), p. 3416-3428
    Abstract: V1 interneurons are inhibitory neurons that play an essential role in vertebrate locomotion. The molecular mechanisms underlying their genesis remain, however, largely undefined. Here, we show that the transcription factor Prdm12 is selectively expressed in p1 progenitors of the hindbrain and spinal cord in the frog embryo, and that a similar restricted expression profile is observed in the nerve cord of other vertebrates as well as of the cephalochordate amphioxus. Using frog, chick and mice, we analyzed the regulation of Prdm12 and found that its expression in the caudal neural tube is dependent on retinoic acid and Pax6, and that it is restricted to p1 progenitors, due to the repressive action of Dbx1 and Nkx6-1/2 expressed in the adjacent p0 and p2 domains. Functional studies in the frog, including genome-wide identification of its targets by RNA-seq and ChIP-Seq, reveal that vertebrate Prdm12 proteins act as a general determinant of V1 cell fate, at least in part, by directly repressing Dbx1 and Nkx6 genes. This probably occurs by recruiting the methyltransferase G9a, an activity that is not displayed by the amphioxus Prdm12 protein. Together, these findings indicate that Prdm12 promotes V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes, and suggest that this function might have only been acquired after the split of the vertebrate and cephalochordate lineages.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    URL: Article
    DOI: 10.1242/dev.121871
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2015
    detail.hit.zdb_id: 2007916-3
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  • 2
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    Online Resource
    XSEB4R, a novel RNA-binding protein involved in retinal cell differentiation downstream of bHLH proneural genes
    The Company of Biologists ; 2004
    In:  Development Vol. 131, No. 4 ( 2004-02-15), p. 851-862
    Details
    In: Development, The Company of Biologists, Vol. 131, No. 4 ( 2004-02-15), p. 851-862
    Abstract: RNA-binding proteins play key roles in the post-transcriptional regulation of gene expression but so far they have not been studied extensively in the context of developmental processes. We report on the molecular cloning and spatio-temporal expression of a novel RNA-binding protein, XSEB4R, which is strongly expressed in the nervous system. This study is focused on the analysis of Xseb4R in the context of primary neurogenesis and retinogenesis. To study Xseb4R function during eye development, we set up a new protocol allowing in vivo lipofection of antisense morpholino oligonucleotides into the retina. The resulting XSEB4R knockdown causes an impairment of neuronal differentiation, with an increase in the number of glial cells. By contrast, our gain-of-function analysis demonstrates that Xseb4R strongly promotes neural differentiation. We also showed a similar function during primary neurogenesis. Consistent with this proneural effect, we found that in the open neural plate Xseb4R expression is upregulated by the proneural gene XNgnr1, as well as by the differentiation gene XNeuroD, but is inhibited by the Notch/Delta pathway. Altogether, our results suggest for the first time a proneural effect for a RNA-binding protein involved in the genetic network of retinogenesis.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    URL: Article
    DOI: 10.1242/dev.00983
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2004
    detail.hit.zdb_id: 2007916-3
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  • 3
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    Online Resource
    The Notch-effector HRT1 gene plays a role in glomerular development and patterning of the Xenopus pronephros anlagen
    The Company of Biologists ; 2006
    In:  Development Vol. 133, No. 15 ( 2006-08-01), p. 2961-2971
    Details
    In: Development, The Company of Biologists, Vol. 133, No. 15 ( 2006-08-01), p. 2961-2971
    Abstract: Notch signaling has been shown to play a role in cell fate decisions in the Xenopus pronephros anlagen. Here, we show that the XenopusHairy-related transcription factor (HRT) gene XHRT1, and the Hairy/Enhancer of split (HES) genes Xhairy1, Xhairy2b, esr9and esr10, have distinct restricted dynamic expression patterns during pronephros development, and that their expression is regulated by Notch. XHRT1, which is the earliest and strongest gene expressed in the pronephric region, is initially transcribed predominantly in the forming glomus, where it is downregulated by antisense morpholino oligonucleotide inhibition of xWT1. Later, it is activated in the most dorsoanterior part of the pronephros anlagen that gives rise to the proximal tubules. In agreement with this dynamic expression profile, we found that early activation of Notch favors glomus, whereas only later activation promotes proximal tubule formation. We show that, among the bHLH-O factors tested, only XHRT1 efficiently inhibits distal tubule and duct formation, and that only its translational inhibition causes a reduction of the expression of proximal tubule and glomus markers. Using domain swap experiments, we found that the XHRT1 C-terminal region is crucial for its activity. Together, our results provide evidence that XHRT1 plays an important role in glomerular development and early proximodistal patterning that is distinct from those of the other pronephric bHLH repressors.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    URL: Article
    DOI: 10.1242/dev.02458
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2006
    detail.hit.zdb_id: 2007916-3
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  • 4
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    Online Resource
    Retinoic acid induced expression of Hnf1β and Fzd4 is required for pancreas development in Xenopus laevis
    The Company of Biologists ; 2018
    In:  Development
    Details
    In: Development, The Company of Biologists
    Abstract: Retinoic acid (RA) is required for pancreas specification in Xenopus and other vertebrates. However, the gene network that is directly induced by RA-signalling in this context remains to be defined. We identified the transcription factor Hnf1β and the Wnt-receptor Fzd4/Fzd4s as direct RA-target genes through RNA-sequencing of in vitro generated pancreatic explants. Functional analyses of Hnf1β and Fzd4/Fzd4s in programmed pancreatic explants and whole embryos revealed their requirement for pancreatic progenitor formation and differentiation. Hnf1β and Fzd4/Fzd4s thus appear to be involved in pre-patterning events of the embryonic endoderm allowing for pancreas formation.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    URL: Article
    DOI: 10.1242/dev.161372
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2018
    detail.hit.zdb_id: 2007916-3
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  • 5
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    Online Resource
    Characterization and function of the bHLH-O protein XHes2: insight into the mechanisms controlling retinal cell fate decision
    The Company of Biologists ; 2006
    In:  Development Vol. 133, No. 20 ( 2006-10-15), p. 4097-4108
    Details
    In: Development, The Company of Biologists, Vol. 133, No. 20 ( 2006-10-15), p. 4097-4108
    Abstract: Neurons and glial cells differentiate from common multipotent precursors in the vertebrate retina. We have identified a novel member of the hairy/Enhancer of split [E(spl)] gene family in Xenopus,XHes2, as a regulator to bias retinal precursor cells towards a glial fate. XHes2 expression is predominantly restricted to sensory organ territories, including the retina. Using in vivo lipofection in the optic vesicle, we found that XHes2 overexpression dramatically increases gliogenesis at the expense of neurogenesis. This increase in glial cells correlates with a delayed cell cycle withdrawal of some retinal progenitors. In addition, birthdating experiments suggest that XHes2 deviates some early born cell types towards a glial fate that would normally have given rise to neurons. Conversely, a significant inhibition of glial differentiation is observed upon XHes2 loss of function. The gliogenic activity of XHes2 relies on its ability to inhibit neuronal differentiation by at least two distinct mechanisms: it not only negatively regulates XNgnr1 and NeuroD transcription, but it also physically interacts with a subset of proneural bHLH proteins.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    URL: Article
    DOI: 10.1242/dev.02567
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2006
    detail.hit.zdb_id: 2007916-3
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  • 6
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    Online Resource
    Evidence for overlapping, but not identical, protein machineries operating in vegetal RNA localization along early and late pathways in Xenopus oocytes
    The Company of Biologists ; 2004
    In:  Development Vol. 131, No. 17 ( 2004-09-01), p. 4263-4273
    Details
    In: Development, The Company of Biologists, Vol. 131, No. 17 ( 2004-09-01), p. 4263-4273
    Abstract: RNAs that localize to the vegetal cortex of Xenopus oocytes are involved in early embryonic patterning and cell fate specification. Two mechanistically distinct pathways lead to RNA enrichment at the vegetal cortex: the early and the late. While several candidate proteins that seem to operate in the late localization pathway have been identified, proteins involved in the early pathway remain to be identified. In this study, we report on the isolation of a novel vegetally localized RNA in Xenopusoocytes that makes use of the early pathway and encodes a protein with a conserved but functionally uncharacterized NIF-motif. The localization signal of XNIF was mapped to a 300-nucleotide region in the 5′-UTR, which is able to mediate both accumulation to the mitochondrial cloud in stage I oocytes, as well as vegetal transport in later stage oocytes. The XNIF-LE contains 16 copies of the previously defined CAC-containing signal motifs for RNA localization. A critical number of such repeats seems to be required for accumulation in the mitochondrial cloud along the early pathway, but additional repeats seem to be required for localization along the late pathway. Cross-linking experiments identify two novel proteins of 62 and 64 kDa that interact with the XNIF-LE but not with the Vg1-LE that operates in the late pathway. Conversely, at least two of the previously identified VgRBPs, Vg1RBP1 and Prrp, also bind to the XNIF-LE. Thus, overlapping, but not identical, protein machineries mediate vegetal RNA localization along early and late pathways in Xenopus oocytes.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    URL: Article
    DOI: 10.1242/dev.01283
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2004
    detail.hit.zdb_id: 2007916-3
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  • 7
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    Online Resource
    Vax1 is a novel homeobox-containing gene expressed in the developing anterior ventral forebrain
    The Company of Biologists ; 1998
    In:  Development Vol. 125, No. 14 ( 1998-07-15), p. 2599-2610
    Details
    In: Development, The Company of Biologists, Vol. 125, No. 14 ( 1998-07-15), p. 2599-2610
    Abstract: The vertebrate forebrain is formed at the rostral end of the neural plate under the regulation of local and specific signals emanating from both the endomesoderm and neuroectoderm. The development of the rostral and ventral forebrain in particular was difficult to study, mainly because no specific markers are available to date. Here, we report the identification of Vax1, a novel homeobox-containing gene identified in mouse, Xenopus and human. It is closely related to members of the Not and Emx gene families, all of which are required for the formation of structures where they are expressed. In mouse and Xenopus, Vax1 expression first occurs in the rostral neural plate, in the medial anterior neural ridge and adjacent ectoderm. Later, at midgestation in the mouse and tadpole stage in Xenopus, the expression remains confined in the derivatives of this territory which differentiate into rostromedial olfactory placode, optic nerve and disc, and anterior ventral forebrain. Together, these observations suggest that Vax1 could have an early evolutionary origin and could participate in the specification and formation of the rostral and ventral forebrain in vertebrates. Comparison of the limits of the expression territory of Vax1 with that of Dlx1, Pax6 and Emx1 indicates that the corticostriatal ridge is a complex structure with distinct identifiable genetic compartments. Besides, the study of Vax1 expression in Pax6-deficient homozygous brains indicates that its regulation is independent of Pax6, although the expression patterns of these two genes appear complementary in wild-type animals. Vax1 chromosomal location is mapped at the distal end of the mouse chromosome 19, linked with that of Emx2. These two genes may have arisen by tandem duplication. The Vax1 gene is thus an interesting new tool to study the rostral ventral forebrain patterning, morphogenesis and evolution as well as the terminal differentiation of the forebrain in mouse and Xenopus.
    Type of Medium: Online Resource
    ISSN: 0950-1991 , 1477-9129
    URL: Article
    DOI: 10.1242/dev.125.14.2599
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 1998
    detail.hit.zdb_id: 2007916-3
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  • 8
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    Online Resource
    Migratory and adhesive properties of Xenopus laevis primordial germ cells in vitro
    The Company of Biologists ; 2013
    In:  Biology Open Vol. 2, No. 12 ( 2013-12-15), p. 1279-1287
    Details
    In: Biology Open, The Company of Biologists, Vol. 2, No. 12 ( 2013-12-15), p. 1279-1287
    Abstract: The directional migration of primordial germ cells (PGCs) to the site of gonad formation is an advantageous model system to study cell motility. The embryonic development of PGCs has been investigated in different animal species, including mice, zebrafish, Xenopus and Drosophila. In this study we focus on the physical properties of Xenopus laevis PGCs during their transition from the passive to the active migratory state. Pre-migratory PGCs from Xenopus laevis embryos at developmental stages 17–19 to be compared with migratory PGCs from stages 28–30 were isolated and characterized in respect to motility and adhesive properties. Using single-cell force spectroscopy, we observed a decline in adhesiveness of PGCs upon reaching the migratory state, as defined by decreased attachment to extracellular matrix components like fibronectin, and a reduced adhesion to somatic endodermal cells. Data obtained from qPCR analysis with isolated PGCs reveal that down-regulation of E-cadherin might contribute to this weakening of cell-cell adhesion. Interestingly, however, using an in vitro migration assay, we found that movement of X. laevis PGCs can also occur independently of specific interactions with their neighboring cells. The reduction of cellular adhesion during PGC development is accompanied by enhanced cellular motility, as reflected in increased formation of bleb-like protrusions and inferred from electric cell-substrate impedance sensing (ECIS) as well as time-lapse image analysis. Temporal alterations in cell shape, including contraction and expansion of the cellular body, reveal a higher degree of cellular dynamics for the migratory PGCs in vitro.
    Type of Medium: Online Resource
    ISSN: 2046-6390
    URL: Article
    DOI: 10.1242/bio.20135140
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2013
    detail.hit.zdb_id: 2632264-X
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  • 9
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    Online Resource
    The Xenopus homologue of the Drosophila gene tailless has a function in early eye development
    The Company of Biologists ; 1998
    In:  Development Vol. 125, No. 13 ( 1998-07-01), p. 2425-2432
    Details
    In: Development, The Company of Biologists, Vol. 125, No. 13 ( 1998-07-01), p. 2425-2432
    Abstract: Genetic circuits responsible for the development of photoreceptive organs appear to be evolutionarily conserved. Here, the Xenopus homologue Xtll of the Drosophila gene tailless (tll), which we find to be expressed during early eye development, is characterized with respect to its relationship to vertebrate regulators of eye morphogenesis, such as Pax6 and Rx. Expression of all three genes is first detected in the area corresponding to the eye anlagen within the open neural plate in partially overlapping, but not identical, patterns. During the evagination of the optic vesicle, Xtll expression is most prominent in the optic stalk, as well as in the distal tip of the forming vesicle. In tadpole-stage embryos, Xtll gene transcription is most prominent in the ciliary margin of the optic cup. Inhibition of Xtll function in Xenopus embryos interferes specifically with the evagination of the eye vesicle and, in consequence, Xpax6 gene expression is severely reduced in such manipulated embryos. These findings suggest that Xtll serves an important regulatory function in the earliest phases of vertebrate eye development.
    Type of Medium: Online Resource
    ISSN: 0950-1991 , 1477-9129
    URL: Article
    DOI: 10.1242/dev.125.13.2425
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 1998
    detail.hit.zdb_id: 2007916-3
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  • 10
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    Online Resource
    A novel function for Hedgehog signalling in retinal pigment epithelium differentiation
    The Company of Biologists ; 2003
    In:  Development Vol. 130, No. 8 ( 2003-04-15), p. 1565-1577
    Details
    In: Development, The Company of Biologists, Vol. 130, No. 8 ( 2003-04-15), p. 1565-1577
    Abstract: Sonic hedgehog is involved in eye field separation along the proximodistal axis. We show that Hh signalling continues to be important in defining aspects of the proximodistal axis as the optic vesicle and optic cup mature. We show that two other Hedgehog proteins, Banded hedgehog and Cephalic hedgehog,related to the mouse Indian hedgehog and Desert hedgehog, respectively, are strongly expressed in the central retinal pigment epithelium but excluded from the peripheral pigment epithelium surrounding the ciliary marginal zone. By contrast, downstream components of the Hedgehog signalling pathway, Gli2,Gli3 and X-Smoothened, are expressed in this narrow peripheral epithelium. We show that this zone contains cells that are in the proliferative state. This equivalent region in the adult mammalian eye, the pigmented ciliary epithelium, has been identified as a zone in which retinal stem cells reside. These data, combined with double labelling and the use of other retinal pigment epithelium markers, show that the retinal pigment epithelium of tadpole embryos has a molecularly distinct peripheral to central axis. In addition, Gli2, Gli3 and X-Smoothened are also expressed in the neural retina, in the most peripheral region of the ciliary marginal zone, where retinal stem cells are found in Xenopus,suggesting that they are good markers for retinal stem cells. To test the role of the Hedgehog pathway at different stages of retinogenesis, we activated the pathway by injecting a dominant-negative form of PKA or blocking it by treating embryos with cyclopamine. Embryos injected or treated at early stages display clear proximodistal defects in the retina. Interestingly, the main phenotype of embryos treated with cyclopamine at late stages is a severe defect in RPE differentiation. This study thus provides new insights into the role of Hedgehog signalling in the formation of the proximodistal axis of the eye and the differentiation of retinal pigment epithelium.
    Type of Medium: Online Resource
    ISSN: 1477-9129 , 0950-1991
    URL: Article
    DOI: 10.1242/dev.00391
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2003
    detail.hit.zdb_id: 2007916-3
    SSG: 12
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