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Negative feedback in the bone morphogenetic protein 4 (BMP4) synexpression group governs its dynamic signaling range and canalizes development

What makes embryogenesis a robust and canalized process is an important question in developmental biology. A bone morphogenetic protein (BMP) morphogen gradient plays a key role in embryonic development, and we are beginning to understand how the self-regulating properties of its signaling circuitry...

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Main Authors: Paulsen, Malte (Author) , Legewie, Stefan (Author) , Eils, Roland (Author) , Karaulanov, Emil (Author) , Niehrs, Christof (Author)
Format: Article (Journal)
Language:English
Published: 01 June, 2011
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2011, Volume: 108, Issue: 25, Pages: 10202-10207
ISSN:1091-6490
DOI:10.1073/pnas.1100179108
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.1100179108
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Author Notes:Malte Paulsen, Stefan Legewie, Roland Eils, Emil Karaulanov, and Christof Niehrs

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245 1 0 |a Negative feedback in the bone morphogenetic protein 4 (BMP4) synexpression group governs its dynamic signaling range and canalizes development  |c Malte Paulsen, Stefan Legewie, Roland Eils, Emil Karaulanov, and Christof Niehrs 
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520 |a What makes embryogenesis a robust and canalized process is an important question in developmental biology. A bone morphogenetic protein (BMP) morphogen gradient plays a key role in embryonic development, and we are beginning to understand how the self-regulating properties of its signaling circuitry ensure robust embryonic patterning. An unexplored question is why the BMP signaling circuit is organized as a modular synexpression group, with a prevalence of feedback inhibitors. Here, we provide evidence from direct experimentation and mathematical modeling that the synexpressed feedback inhibitors BAMBI, SMAD6, and SMAD7 (i) expand the dynamic BMP signaling range essential for proper embryonic patterning and (ii) reduce interindividual phenotypic and molecular variability in Xenopus embryos. Thereby, negative feedback linearizes signaling responses and confers robust patterning, thus promoting canalized development. The presence of negative feedback inhibitors in other growth factor synexpression groups suggests that these properties may constitute a general principle. 
650 4 |a Animals 
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650 4 |a Feedback, Physiological 
650 4 |a Gene Expression Regulation, Developmental 
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650 4 |a HEK293 Cells 
650 4 |a Humans 
650 4 |a Membrane Proteins 
650 4 |a Models, Theoretical 
650 4 |a Signal Transduction 
650 4 |a Smad6 Protein 
650 4 |a Smad7 Protein 
650 4 |a Xenopus laevis 
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