Additional sex combs affects antennal development by means of spatially restricted repression of Antp and Wg

Halachmi, Naomi; Schulze, Karen L.; Inbal, Adi; Salzberg, Adi

doi:10.1002/dvdy.21239

Cited by 9 publications

(7 citation statements)

References 67 publications

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“…Detection of lacZ reporter expression was carried out using anti-β-galactosidase (Promega, #Z378A). Sal was detected with rabbit α-Sal (Halachmi et al, 2007) (gift from A. Salzberg, Technion-Israel Institute of Technology, Haifa, Israel). Secondaries antibodies used for fluorescence microscopy were conjugated with AlexaFluor 488, 568 or 647 (Invitrogen).…”

Section: Immunohistochemistry and Microscopymentioning

confidence: 99%

Activin receptor inhibition by Smad2 regulates Drosophila wing disc patterning through BMP-response elements

Peterson

O’Connor

2013

Development

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SUMMARYImaginal disc development in Drosophila requires coordinated cellular proliferation and tissue patterning. In our studies of TGF 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 TGF 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.

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Section: Immunohistochemistry and Microscopymentioning

confidence: 99%

Activin receptor inhibition by Smad2 regulates Drosophila wing disc patterning through BMP-response elements

Peterson

O’Connor

2013

Development

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“…The specific primary antibodies used were: mouse anti-b-gal (1:1000; Promega), rabbit anti-Spalt [1:1000; a gift from A. Salzberg (Halachmi et al, 2007)], rat anti-Nab [1:1000 (Suissa et al, 2011)], rat anti-Brk (1:1000; a gift from F. A. Martín and G. Morata, CDBM University Autonoma De Madrid, Madrid, Spain), rabbit anti-cleaved Caspase 3 (1:40; Cell Signaling) and Rabbit anti-Vg (1:20; a gift from Sean Carroll). Secondary antibodies used: RRX-or Cy5-conjugated (1:400; Jackson Laboratories).…”

Section: Immunohistochemistry and Imagingmentioning

confidence: 99%

Inverse regulation of target genes at the brink of the BMP morphogen activity gradient

Ziv

Finkelstein

Suissa

et al. 2012

Journal of Cell Science

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Summary BMP-dependent patterning in the Drosophila melanogaster wing imaginal disc serves as a paradigm to understand how morphogens specify cell fates. The observed profile of the transcriptional response to the graded signal of BMP relies upon two counter-active gradients of pMad and Brinker (Brk). This patterning model is inadequate to explain the expression of target genes, like vestigial and spalt, in lateral regions of the wing disc where BMP signals decline and Brk levels peak. Here, we show that in contrast to the reciprocal repressor gradient mechanism, where Brk represses BMP targets in medial regions, target expression in lateral regions is downregulated by BMP signalling and activated by Brk. Brk induces lateral expression indirectly, apparently through repression of a negative regulator. Our findings provide a model explaining how the expression of an established BMP target is differentially and inversely regulated along the anterior-posterior axis of the wing disc.

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“…The specific primary antibodies used were: mouse anti-β-gal (1:1000; Promega), rabbit anti-Spalt [1:1000; a gift from A. Salzberg (Halachmi et al, 2007)], rabbit anti-dNAB [1:500; a gift from J. Díaz-Benjumea (Terriente Felix et al, 2007)], rat anti-Brk (1:1000; a gift from F. A. Martín and G. Morata, CDBM University Autonoma De Madrid, Madrid, Spain) and rabbit anti-cleaved Caspase 3 (1:40; Cell Signaling). Images were taken on a TE2000-E confocal microscope (Nikon) using a 203 objective.…”

Section: Immunohistochemistrymentioning

confidence: 99%

The co-regulator dNAB interacts with Brinker to eliminate cells with reduced Dpp signaling

et al. 2009

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The proper development of tissues requires morphogen activity that dictates the appropriate growth and differentiation of each cell according to its position within a developing field. Elimination of underperforming cells that are less efficient in receiving/transducing the morphogenetic signal is thought to provide a general fail-safe mechanism to avoid developmental misspecification. In the developing Drosophila wing, the morphogen Dpp provides cells with growth and survival cues. Much of the regulation of transcriptional output by Dpp is mediated through repression of the transcriptional repressor Brinker (Brk), and thus through the activation of target genes. Mutant cells impaired for Dpp reception or transduction are lost from the wing epithelium. At the molecular level, reduced Dpp signaling results in Brk upregulation that triggers apoptosis through activation of the JNK pathway. Here we show that the transcriptional co-regulator dNAB is a Dpp target in the developing wing that interacts with Brk to eliminate cells with reduced Dpp signaling through the JNK pathway. We further show that both dNAB and Brk are required for cell elimination induced by differential dMyc expression, a process that depends on reduced Dpp transduction in outcompeted cells. We propose a novel mechanism whereby the morphogen Dpp regulates the responsiveness to its own survival signal by inversely controlling the expression of a repressor, Brk, and its co-repressor, dNAB.KEY WORDS: Brinker, Dpp survival signal, Wing development, dMyc (Dm)-induced cell competition, dNAB (Drosophila Nab)

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Additional sex combs affects antennal development by means of spatially restricted repression of Antp and Wg

Cited by 9 publications

References 67 publications

Activin receptor inhibition by Smad2 regulates Drosophila wing disc patterning through BMP-response elements

Activin receptor inhibition by Smad2 regulates Drosophila wing disc patterning through BMP-response elements

Inverse regulation of target genes at the brink of the BMP morphogen activity gradient

The co-regulator dNAB interacts with Brinker to eliminate cells with reduced Dpp signaling

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