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This study analyzes genomic features and expression patterns of NPRs in Drosophila melanogaster using comparative genomics, single-cell RNA sequencing, transcription-factor network analysis, and experimental validation. NPR genes show more complex cis-regulatory landscapes, broader transcription-factor control, and dynamically modulated expression in context, with an NPR-biased pattern and increased expression during aging.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/transcriptional-regulation-of-neuropeptide-receptors-underlies-context-dependent-adaptation-in-drosophila-melanogaster-research-article/439819/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/transcriptional-regulation-of-neuropeptide-receptors-underlies-context-dependent-adaptation-in-drosophila-melanogaster-research-article/439819.png","ImageObject",300,407,{"name":92,"@type":93},"Stanley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What biological problem does the study address?","Question",{"text":112,"@type":113},"How neuropeptide receptors contribute to context-dependent behavioral plasticity in Drosophila melanogaster.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which methods are used to investigate NPR regulation?",{"text":117,"@type":113},"Comparative genomics, single-cell RNA sequencing (scRNA-seq), transcription factor network analysis, and empirical validation including qRT-PCR.",{"name":119,"@type":110,"acceptedAnswer":120},"What key regulatory difference is observed between NPR and NP genes?",{"text":121,"@type":113},"NPR genes have more complex cis-regulatory landscapes with more enhancers and are controlled by a broader network of transcription factors.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},439819,1790778182,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},2336477405376,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","RESEARCH ARTICLE  \nTranscriptional regulation of neuropeptide receptors underlies context-dependent adaptation in Drosophila melanogaster  \nSeungHeui Ryu 1 , Yanan Wei2, Zekun Wu2 , Tianmu Zhang2, DoHoon Lee 1 , Hadi Najafi3  and Woo Jae Kim2,4   \n1 Department of Information Convergence Engineering, Pusan National University, Busan, Korea  \n2 The HIT Center for Life Sciences, Harbin Institute of Technology, Harbin, China  \n3 Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA  \n4 Medical and Health Research Institute, Zhengzhou Research Institute of HIT, Zhengzhou, China  \nKeywords  \nDrosophila melanogaster; neuropeptide; neuropeptide receptor; peptidergic signaling; transcription factor; transcriptional regulation  \nCorrespondence  \nD. Lee, Department of Information Convergence Engineering, Pusan National University, Busan, Korea  \nE-mail: [dohoon@pusan.ac.kr](dohoon@pusan.ac.kr)and  \nH. Najafi, Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA  \nE-mail: hadi. najafi[hajivar@umassmed.edu](hajivar@umassmed.edu)[ ](hajivar@umassmed.edu)and  \nW. J. Kim, The HIT Center for Life Sciences, Harbin Institute of Technology, Harbin, China  \n[E-mail:](E-mail: wkim@hit.edu.cn)[ wkim@hit.edu.cn](E-mail: wkim@hit.edu.cn)  \nSeungHeui Ryu, Yanan Wei and Zekun Wu contributed equally to this work.  \n(Received 10 February 2025, revised 30 July 2025, accepted 7 August 2025)  \nNeuropeptides (NPs) and their receptors (NPRs) play critical roles in modulating physiological processes and behaviors across species. While the transcriptional regulation of NP genes has been extensively studied, how NPRs contribute to context-dependent behavioral plasticity remains poorly understood. Here, we investigate the genomic features and expression patterns of NPRs in Drosophila melanogaster, leveraging comparative genomics, single-cell RNA sequencing (scRNA-seq), transcription factor (TF) network analysis, and empirical validation to uncover the regulatory mechanisms that involve NPRs and play roles in context-dependent adaptation. We demonstrate that NPR genes exhibit more complex cis-regulatory landscapes, with greater numbers of enhancers compared to NP genes. Also, NPRs are regulated via a broader network of TFs, particularly in response to environmental and physiological cues such as temperature shifts. Through analysis of scRNA-seq data and qRT-PCR, we show that the expression level of NPRs is dynamically modulated in a context-dependent manner, while NP levels remain relatively stable. This “NPR-biased” gene regulation is evident across diverse combinations of NP-NPR pairs, with a distinct pattern of TF control in the head and body of D. melanogaster. Furthermore, the expression level of NPR genes increases during aging of the fly, suggesting a key role in aging and developmental processes. Our findings highlight the importance of NPR transcriptional control in shaping neuropeptidergic signaling and adaptive behaviors.  \ndoi:10.1002/2211-5463.70107  \nEdited by So Nakagawa  \nAbbreviations  \nAFCA, aging fly cell atlas; ARRIVE, animal research: reporting of in vivo experiments; AS, alternative splicing; CRM, cis regulatory module; D. melanogaster, Drosophila melanogaster; FCA, fly cell atlas; GPCRs, G-protein coupled receptors; GRN, gene regulatory network; kb, kilobase pairs; NP, neuropeptide; NPR, neuropeptide receptor; qRT-PCR, quantitative reverse transcription PCR; RPKM, Reads Per Kilobase per Million mapped reads; scRNA-seq, single-cell RNA-sequencing; SEM, standard error of the mean; TCC, total cell count; TF, transcription factor; TFBS-HSA, TF binding sites HOT spot analysis; TPM, transcripts per million mapped reads; UMI, unique molecular identifier.  \n90 FEBS Open Bio 16 (2026) 90–115 ª 2025 The Author(s) . FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.  \nThis is an","cbCaijV09dLmdX1f","https://ap.wps.com/l/cbCaijV09dLmdX1f","pdf",5847627,26,"English","# Introduction\n## Neuropeptides and neuropeptide receptors in adaptation\n## Rationale and study focus","[{\"question\":\"What biological problem does the study address?\",\"answer\":\"How neuropeptide receptors contribute to context-dependent behavioral plasticity in Drosophila melanogaster.\"},{\"question\":\"Which methods are used to investigate NPR regulation?\",\"answer\":\"Comparative genomics, single-cell RNA sequencing (scRNA-seq), transcription factor network analysis, and empirical validation including qRT-PCR.\"},{\"question\":\"What key regulatory difference is observed between NPR and NP genes?\",\"answer\":\"NPR genes have more complex cis-regulatory landscapes with more enhancers and are controlled by a broader network of transcription factors.\"}]","Transcriptional regulation of neuropeptide receptors underlies context-dependent adaptation in Drosophila melanogaster - Research Article | PDF",1790690308,66]