Dichotomous cis-regulatory motifs mediate the maturation of the neuromuscular junction by retrograde BMP signaling.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
23 09 2022
23 09 2022
Historique:
accepted:
19
08
2022
revised:
20
07
2022
received:
12
02
2022
pubmed:
28
8
2022
medline:
28
9
2022
entrez:
27
8
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36029115
pii: 6677560
doi: 10.1093/nar/gkac730
pmc: PMC9508838
doi:
Substances chimiques
Bone Morphogenetic Proteins
0
Drosophila Proteins
0
Transforming Growth Factor beta
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
9748-9764Subventions
Organisme : CIHR
ID : F16-01394
Pays : Canada
Organisme : NINDS NIH HHS
ID : R01 NS082793
Pays : United States
Organisme : CIHR
ID : F20-04798
Pays : Canada
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.
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