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Article . 2012 . Peer-reviewed
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Article . 2009 . Peer-reviewed
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A BMP-Shhnegative-feedback loop restrictsShhexpression during limb development

Authors: Bastida, M. Félix; Sheth, Rushikesh; Ros, María A.;

A BMP-Shhnegative-feedback loop restrictsShhexpression during limb development

Abstract

Normal patterning of tissues and organs requires the tight restriction of signaling molecules to well-defined organizing centers. In the limb bud, one of the main signaling centers is the zone of polarizing activity (ZPA) that controls growth and patterning through the production of sonic hedgehog (SHH). The appropriate temporal and spatial expression of Shh is crucial for normal limb bud patterning, because modifications, even if subtle, have important phenotypic consequences. However, although there is a lot of information about the factors that activate and maintain Shhexpression, much less is known about the mechanisms that restrict its expression to the ZPA. In this study, we show that BMP activity negatively regulates Shh transcription and that a BMP-Shhnegative-feedback loop serves to confine Shh expression. BMP-dependent downregulation of Shh is achieved by interfering with the FGF and Wnt signaling activities that maintain Shh expression. We also show that FGF induction of Shh requires protein synthesis and is mediated by the ERK1/2 MAPK transduction pathway. BMP gene expression in the posterior limb bud mesoderm is positively regulated by FGF signaling and finely regulated by an auto-regulatory loop. Our study emphasizes the intricacy of the crosstalk between the major signaling pathways in the posterior limb bud.

Country
Spain
Keywords

Limb Buds, ZPA, Down-Regulation, Chick Embryo, SHH, Mesoderm, FGF signaling, Mice, Noggin, BMP, Animals, Hedgehog Proteins, Limb development, Cell Death, Gene Expression Regulation, Developmental, Extremities, Wnt signaling, Fibroblast Growth Factors, Protein Biosynthesis, Bone Morphogenetic Proteins, Pattern formation, Signal Transduction

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
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OpenAIRE UsageCountsDownloads provided by UsageCounts
76
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145
258
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bronze