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Integration of Shh and Fgf signaling in controlling Hox gene expression in cultured limb cells

Rodrigues, Alan R
Yakushiji-Kaminatsui, Nayuta
Atsuta, Yuji
Tabin, Clifford J
Published in Proceedings of the National Academy of Sciences. 2017, vol. 114, no. 12, p. 3139-3144
Abstract During embryonic development, fields of progenitor cells form complex structures through dynamic interactions with external signaling molecules. How complex signaling inputs are integrated to yield appropriate gene expression responses is poorly understood. In the early limb bud, for instance, Sonic hedgehog (Shh) is expressed in the distal posterior mesenchyme, where it acts as a mediator of anterior to posterior (AP) patterning, whereas fibroblast growth factor 8 (Fgf8) is produced by the apical ectodermal ridge (AER) at the distal tip of the limb bud to direct outgrowth along the proximal to distal (PD) axis. Here we use cultured limb mesenchyme cells to 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 activate 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 only partially achieved under these in vitro conditions, suggesting an additional requirement for other factors.
Keywords AnimalsCellsCulturedChick EmbryoChromatin ImmunoprecipitationExtremities/embryologyFibroblast Growth Factors/metabolismGene Expression RegulationDevelopmentalGenesHomeoboxHedgehog Proteins/metabolismHigh-Throughput Nucleotide SequencingLigandsProtein BindingSignal TransductionStem Cells/cytology/metabolism
PMID: 28270602
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Article (Published version) (1 MB) - public document Free access
Research groups Groupe Duboule
Contrôle épigénétique du développement embryonnaire (999)
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RODRIGUES, Alan R et al. Integration of Shh and Fgf signaling in controlling Hox gene expression in cultured limb cells. In: Proceedings of the National Academy of Sciences, 2017, vol. 114, n° 12, p. 3139-3144. doi: 10.1073/pnas.1620767114 https://archive-ouverte.unige.ch/unige:116900

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Deposited on : 2019-05-03

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