Integration of Shh and Fgf signaling in controlling Hox expression in cultured limb cells
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PROVIDER: PRJNA358040 | ENA |
REPOSITORIES: ENA
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Project description:During embryonic development, fields of progenitor cells form complex spatial structures through dynamic interactions with external signaling molecules. However, how complex signaling inputs are integrated to yield appropriate gene expression responses is poorly understood. For instance several critical signals have been well characterized in the early limb bud, including Sonic hedgehog (Shh) and Fibroblast growth Factor 8 (Fgf8). While the former is expressed in the distal posterior mesenchyme where it acts as the mediator of anterior to posterior (AP) patterning, the latter is produced by the apical ectodermal ridge (AER) at the distal tip of the limb bud and directs the outgrowth and the proximal to distal (PD) organization of the limb. Here we use cultured limb mesenchyme cells to try and assess the response of the target Hoxd genes to these two factors. We find that they act synergistically and that both factors are required to get activation of Hoxd13 in limb mesenchymal cells. However, the analysis of the enhancer landscapes flanking the HoxD cluster reveals that the bimodal regulatory switch observed in vivo is not fully achieved under these in vitro conditions, suggesting the requirement for other factors.
2017-03-06 | GSE92556 | GEO
Project description:During embryonic development, fields of progenitor cells form complex spatial structures through dynamic interactions with external signaling molecules. However, how complex signaling inputs are integrated to yield appropriate gene expression responses is poorly understood. For instance several critical signals have been well characterized in the early limb bud, including Sonic hedgehog (Shh) and Fibroblast growth Factor 8 (Fgf8). While the former is expressed in the distal posterior mesenchyme where it acts as the mediator of anterior to posterior (AP) patterning, the latter is produced by the apical ectodermal ridge (AER) at the distal tip of the limb bud and directs the outgrowth and the proximal to distal (PD) organization of the limb. Here we use cultured limb mesenchyme cells to try and assess the response of the target Hoxd genes to these two factors. We find that they act synergistically and that both factors are required to get activation of Hoxd13 in limb mesenchymal cells. However, the analysis of the enhancer landscapes flanking the HoxD cluster reveals that the bimodal regulatory switch observed in vivo is not fully achieved under these in vitro conditions, suggesting the requirement for other factors.
2017-03-06 | GSE92555 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-03-06 | GSE92557 | GEO
Project description:Development of the complex structure of the vertebrate limb requires carefully orchestrated interactions between multiple regulatory pathways and proteins. Among these, precise regulation of 5’ Hox transcription factor expression is essential for proper limb bud patterning and development. Here, we identified Geminin (Gmnn) as a novel regulator of this process. A conditional model of Gmnn deficiency resulted in loss or severe reduction of forelimb skeletal elements, while both the forelimb autopod and hindlimb were unaffected. 5’ Hox gene expression expanded into more proximal and anterior regions of embryonic forelimb buds in this Gmnn-deficient model. A second conditional model of Gmnn deficiency instead caused a similar but less severe reduction of hindlimb skeletal elements and hindlimb polydactyly, while not affecting the forelimb. An ectopic posterior Shh signaling center was evident in the anterior hindlimb bud of Gmnn-deficient embryos in this model. This center ectopically expressed Hoxd13, the Hoxd13 target Shh, and the Shh target Ptch1, while these mutant hindlimb buds also had reduced levels of the cleaved, repressor form of Gli3, a Shh pathway antagonist. Together, this work delineates a new role for Gmnn in modulating Hox expression to pattern the vertebrate limb.
2020-06-05 | GSE143211 | GEO
Project description:Multiple genes are dysregulated in hindlimb buds of Nipbl-deficient embryos. In all, more than 1000 limb bud genes were found to be significantly altered in expression by microarray analysis of E10.5 mouse hindlimb buds. Small changes in expression (mostly decreases) were observed for genes involved in FGF, BMP, and SHH pathways, as well as numerous genes involved in the Wnt/planar cell polarity signaling pathway. Genes involved in the Mediator complex, Cohesin function, and Hox gene expression and functions were also dysregulated in Nipbl deficient limb buds. Microarray analysis using RNA extracted from E10.5 hindlimb limb buds harvested from stage-matched Nipbl+/- (n=12) and wildtype (n=12)
2014-08-30 | E-GEOD-60932 | biostudies-arrayexpress
Project description:During limb development, fibroblast growth factors (FGFs) govern proximal-distal outgrowth and patterning. FGFs also synchronize developmental patterning between the proximal-distal and anterior-posterior axes by maintaining sonic hedgehog (SHH) expression in cells of the zone of polarizing activity (ZPA) in the distal posterior mesoderm. SHH, in turn, maintains FGFs in the apical ectodermal ridge (AER) which caps the distal tip of the limb bud. Crosstalk between FGF and SHH signaling is critical for patterned limb development, but the mechanisms underlying this feedback loop are not well characterized. Implantation of FGF beads in the proximal posterior limb bud can maintain SHH expression in the former ZPA domain (evident 3hrs after application), while prolonged exposure (24hrs) can induce SHH outside of this domain. Although temporally and spatially disparate, comparative analysis of transcriptome data from these different populations enriched molecules required for FGF-mediated SHH regulation.
2018-12-18 | GSE114661 | GEO
Project description:Multiple genes are dysregulated in hindlimb buds of Nipbl-deficient embryos. In all, more than 1000 limb bud genes were found to be significantly altered in expression by microarray analysis of E10.5 mouse hindlimb buds. Small changes in expression (mostly decreases) were observed for genes involved in FGF, BMP, and SHH pathways, as well as numerous genes involved in the Wnt/planar cell polarity signaling pathway. Genes involved in the Mediator complex, Cohesin function, and Hox gene expression and functions were also dysregulated in Nipbl deficient limb buds.
2014-08-30 | GSE60932 | GEO
Project description:Purpose: The response to Hedgehog signaling in the limb is driven by GLI bound enhancers. While most Hh targets in the developing limb bud appear to be regulated by the activity of GLI-repressor, the role of GLI activator in this regulation is unclear. Here we assess the roles of GLI activator and repressor in regulating H3K27ac to activate their enhancers. Methods: ChIP-seq was performed in Embryonic day 10.5 mouse limb buds from WT, Shh-/- and Shh-/-Gli3-/- embryos Results: We found that most GLI binding regions can be activated in the absence of both GLI activator and repressor, while a small subset require GLI activator for activity. These indicate that most GLI enhancers in the limb are regulated by GLI repression.
2020-01-21 | GSE133712 | GEO
Project description:The transcriptome of mouse limb buds of Shh mutant embryos was compared to the transcriptome of limb buds of wild type embryos at embryonic day E10.5
2011-05-01 | E-MEXP-3142 | biostudies-arrayexpress
Project description:During limb development, in addition to proximal to distal outgrowth, FGF regulates a number of factors necessary for SHH expression. To elucidate the molecules involved in FGF-mediated SHH expression we implanted FGF2 beads in HH23 chicken forelimb buds and excised the SHH-expressing tissue for transcriptome analysis. The hypothesis is that this transcriptome data along with data from SHH-expressing tissue after a 24hr treatment would highlight molecules necessary for SHH FGF-mediated SHH expression. Results from the overlap provide a short-list of SHH-related genes which require further testing to assess their role in mediating SHH expression.
2018-12-18 | GSE114662 | GEO