|Activin receptor inhibition by Smad2 regulates Drosophila wing disc patterning through BMP-response elements.|
|PMID: 23293296 Owner: NLM Status: MEDLINE|
|Imaginal disc development in Drosophila requires coordinated cellular proliferation and tissue patterning. In our studies of TGFβ superfamily signaling components, we found that a protein null mutation of Smad2, the only Activin subfamily R-Smad in the fruit fly, produces overgrown wing discs that resemble gain of function for BMP subfamily signaling. The wing discs are expanded specifically along the anterior-posterior axis, with increased proliferation in lateral regions. The morphological defect is not observed in mutants for the TGFβ receptor baboon, and epistasis tests showed that baboon is epistatic to Smad2 for disc overgrowth. Rescue experiments indicate that Baboon binding, but not canonical transcription factor activity, of Smad2 is required for normal disc growth. Smad2 mutant discs generate a P-Mad stripe that is narrower and sharper than the normal gradient, and activation targets are correspondingly expressed in narrowed domains. Repression targets of P-Mad are profoundly mis-regulated, with brinker and pentagone reporter expression eliminated in Smad2 mutants. Loss of expression requires a silencer element previously shown to be controlled by BMP signaling. Epistasis experiments show that Baboon, Mad and Schnurri are required to mediate the ectopic silencer output in the absence of Smad2. Taken together, our results show that loss of Smad2 permits promiscuous Baboon activity, which represses genes subject to control by Mad-dependent silencer elements. The absence of Brinker and Pentagone in Smad2 mutants explains the compound wing disc phenotype. Our results highlight the physiological relevance of substrate inhibition of a kinase, and reveal a novel interplay between the Activin and BMP pathways.|
|Aidan J Peterson; Michael B O'Connor|
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|Type: Journal Article; Research Support, N.I.H., Extramural|
|Title: Development (Cambridge, England) Volume: 140 ISSN: 1477-9129 ISO Abbreviation: Development Publication Date: 2013 Feb|
|Created Date: 2013-01-07 Completed Date: 2013-03-07 Revised Date: 2014-04-08|
Medline Journal Info:
|Nlm Unique ID: 8701744 Medline TA: Development Country: England|
|Languages: eng Pagination: 649-59 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Bone Morphogenetic Proteins / metabolism
Drosophila / genetics, metabolism*, physiology
Drosophila Proteins / genetics, metabolism*
Extracellular Matrix Proteins / genetics, metabolism
Gene Expression Regulation, Developmental*
Imaginal Discs / metabolism, physiology*
Receptors, Transforming Growth Factor beta / genetics, metabolism
Repressor Proteins / genetics, metabolism
Smad2 Protein / genetics, metabolism*
Wing / metabolism, physiology*
|R01 GM095746/GM/NIGMS NIH HHS; R01 GM95746/GM/NIGMS NIH HHS|
|0/Bone Morphogenetic Proteins; 0/Drosophila Proteins; 0/Extracellular Matrix Proteins; 0/Magu protein, Drosophila; 0/Receptors, Transforming Growth Factor beta; 0/Repressor Proteins; 0/Smad2 Protein; 0/Smad2 protein, Drosophila; 0/brinker protein, Drosophila; EC 126.96.36.199/Activin Receptors; EC 188.8.131.52/Babo protein, Drosophila|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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