bantam microRNA is a negative regulator of the Drosophila decapentaplegic pathway

Abstract

Decapentaplegic (Dpp), the Drosophila homolog of the vertebrate bone morphogenetic protein (BMP2/4), is crucial for patterning and growth in many developmental contexts. The Dpp pathway is regulated at many different levels to exquisitely control its activity. We show that bantam (ban), a microRNA, modulates Dpp signaling activity. Over expression of ban decreases phosphorylated Mothers against decapentaplegic (Mad) levels and negatively affects Dpp pathway transcriptional target genes, while null mutant clones of ban upregulate the pathway. We provide evidence that dpp upregulates ban in the wing imaginal disc, and attenuation of Dpp signaling results in a reduction of ban expression, showing that they function in a feedback loop. Furthermore, we show that this feedback loop is important for maintaining anterior-posterior compartment boundary stability in the wing disc through regulation of optomotor blind (omb), a known target of the pathway. Our results support a model that ban functions with dpp in a negative feedback loop.

Regulation of Body Size and Growth Control

“…A major Yorkie target is the microRNA bantam , which is required for Yorkie-driven growth in Drosophila ( Hipfner et al 2002 ; Brennecke et al 2003 ; Nolo et al 2006 ; Thompson and Cohen 2006 ; Peng et al 2009 ). As a microRNA, bantam induces the degradation of complementary target transcripts, and known bantam targets include those encoding Mad ( Robins et al 2005 ; Kane et al 2018 ), Tgi ( Shen et al 2015 ), the apoptosis promoter Hid ( Brennecke et al 2003 ), the transcriptional repressor Capicua ( Herranz et al 2012 ), and the cell cycle inhibitor Tribbles, which blocks the G2/M transition ( Gerlach et al 2019 ). Through its downregulation of these and other targets, bantam promotes cell survival and proliferation.…”

Growth control in the Drosophila wing disk

“…Figure shows that the Dpp signaling pathway is not a simple feed‐forward network—various feedback loops exist. For instance, ban , is down‐regulated by Brk (Martín, Pérez‐Garijo, Moreno, & Morata, ), but at the same time ban represses pMad (Kane, Vora, Padgett, & Li, ; Robins, Li, & Padgett, ). Another Dpp target gene dad binds to Tkv and Sax to inhibit the phosphorylation of Mad (Kamiya, Miyazono, & Miyazawa, ), and this was proposed to play an important role in the maintenance of the robust Dpp activity gradient, as reflected in the level of pMad (Ogiso, Tsuneizumi, Masuda, Sato, & Tabata, ).…”

The Drosophila MLR COMPASS-like complex regulates bantam miRNA expression differentially in the context of cell fate

“…The Tgf-β, Hippo and Notch pathways share a common transcriptional target, the bantam miRNA, and regulation of bantam expression by these pathways is necessary for proper imaginal disc formation (Attisano and Wrana, 2013;Becam et al, 2011;Boulan et al, 2013;Doumpas et al, 2013;Herranz et al, 2012;Kane et al, 2018;Li and Padgett, 2012;Martin et al, 2004;Oh and Irvine, 2011;Oh et al, 2014;Qing et al, 2014;Wu et al, 2017;Zhang et al, 2013). Given the requirement for the MLR complex in regulating targets of these pathways, we hypothesized that the bantam miRNA is a potential direct target of the complex.…”

“…The MLR complex also associates with the Hippo coregulator HCF and signaling effector Yorkie for proper Hippo pathway target gene activation (Nan et al, 2019;Oh et al, 2014). In the fly, these developmental signaling pathways are all linked by the miRNA bantam, which is a direct transcriptional target as well as a feedback regulator of these three pathways (Kane et al, 2018;Oh and Irvine, 2011;Shen et al, 2015;Wu et al, 2017). Defects resulting from alteration of these pathways can be enhanced or rescued through modulation of bantam levels, and bantam modulation alone can phenocopy these effects (which was not certified by peer review) is the author/funder.…”