Dichotomous cis-regulatory motifs mediate the maturation of the neuromuscular junction by retrograde BMP signaling.
Dichotomous cis-regulatory motifs mediate the maturation of the neuromuscular junction by retrograde BMP signaling.
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DOI：
10.1093/nar/gkac730
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发表时间：
2022-09-23
影响因子：
14.9
通讯作者：
Allan, Douglas W.
中科院分区：
文献类型：
--
作者：
Vuilleumier, Robin;Miao, Mo;Medina-Giro, Sonia;Ell, Clara-Maria;Flibotte, Stephane;Lian, Tianshun;Kauwe, Grant;Collins, Annie;Ly, Sophia;Pyrowolakis, George;Haghighi, A. Pejmun;Allan, Douglas W.
Retrograde bone morphogenetic protein (BMP) signaling at the Drosophila neuromuscular junction (NMJ) has served as a paradigm to study TGF-β-dependent synaptic function and maturation. Yet, how retrograde BMP signaling transcriptionally regulates these functions remains unresolved. Here, we uncover a gene network, enriched for neurotransmission-related genes, that is controlled by retrograde BMP signaling in motor neurons through two Smad-binding cis-regulatory motifs, the BMP-activating (BMP-AE) and silencer (BMP-SE) elements. Unpredictably, both motifs mediate direct gene activation, with no involvement of the BMP derepression pathway regulators Schnurri and Brinker. Genome editing of candidate BMP-SE and BMP-AE within the locus of the active zone gene bruchpilot, and a novel Ly6 gene witty, demonstrated the role of these motifs in upregulating genes required for the maturation of pre- and post-synaptic NMJ compartments. Our findings uncover how Smad-dependent transcriptional mechanisms specific to motor neurons directly orchestrate a gene network required for synaptic maturation by retrograde BMP signaling.
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影响因子：
3.7
作者：
Gafner L;Dalessi S;Escher E;Pyrowolakis G;Bergmann S;Basler K
通讯作者：
Basler K
影响因子：
5.8
作者：
Bauer-Mehren, Anna;Rautschka, Michael;Furlong, Laura I.
通讯作者：
Furlong, Laura I.
影响因子：
3.7
作者：
Bauer-Mehren A;Bundschus M;Rautschka M;Mayer MA;Sanz F;Furlong LI
通讯作者：
Furlong LI
影响因子：
5.3
作者：
Berke, Brett;Wittnam, Jessica;Keshishian, Haig
通讯作者：
Keshishian, Haig
影响因子：
14.9
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.