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The spz gene (UniProt accession P48607) encodes Spaetzle (also spelled Spätzle), a secreted cytokine-like signaling protein in Drosophila melanogaster. The protein is produced as a precursor with multiple names including "Protein spaetzle," "Protein spatzle," and its mature processed form "Protein spaetzle C-106" (dine2022functionalcharacterizationof pages 26-32). Spaetzle belongs to the Spätzle family of cystine-knot domain-containing proteins and functions as the canonical extracellular ligand for Toll receptors (saucereau2021structureanddynamics pages 1-3, saucereau2022structureanddynamics pages 1-2).
Spaetzle is not an enzyme. It has no catalytic activity, does not process substrates, and exhibits no enzymatic substrate specificity (saucereau2021structureanddynamics pages 1-3, saucereau2022structureanddynamics pages 1-2, edosa2020tmspz4playsan pages 1-3). Instead, Spaetzle functions as a secreted, cytokine-like signaling ligand that activates Toll receptors through direct protein-protein binding interactions (saucereau2022structureanddynamics pages 1-2, dine2022functionalcharacterizationof pages 26-32, kato2023analysisofthe pages 1-2).
Spaetzle is synthesized as an inactive precursor protein (pro-Spaetzle) with a characteristic domain architecture (saucereau2022structureanddynamics pages 1-2, dine2022functionalcharacterizationof pages 26-32):
The C-106 domain adopts a cystine-knot fold, a compact three-dimensional structure stabilized by disulfide bonds between conserved cysteine residues (saucereau2021structureanddynamics pages 1-3, saucereau2022structureanddynamics pages 1-2, dine2022functionalcharacterizationof pages 26-32). This structural motif is related to vertebrate neurotrophin growth factors such as nerve growth factor and is characteristic of cytokine-like signaling molecules (saucereau2021structureanddynamics pages 1-3, gangloff2021structureanddynamics pages 5-7). The mature, active form exists as a disulfide-linked homodimer with both intra- and interchain disulfide bonds stabilizing the structure (gangloff2021structureanddynamics pages 5-7, dine2022functionalcharacterizationof pages 26-32, miao2024identificationofimmunityrelated pages 8-9).
Spaetzle activation is a tightly regulated proteolytic process. The inactive pro-Spaetzle precursor must undergo extracellular cleavage to generate the active C-terminal ligand (nakano2023damagesensingmediated pages 5-6, dine2022functionalcharacterizationof pages 26-32, shan2023anevolutionarilyconserved pages 6-8). Processing occurs at a specific site near the junction between the prodomain and C-106 domain, typically containing an arginine-valine (Arg-Val) sequence (nakano2023damagesensingmediated pages 5-6).
Different serine proteases activate Spaetzle depending on the biological context (nakano2023damagesensingmediated pages 5-6, dine2022functionalcharacterizationof pages 26-32, shan2023anevolutionarilyconserved pages 6-8):
During Embryonic Development:
- Easter: The principal terminal protease that cleaves pro-Spaetzle during embryonic dorsoventral patterning (dine2022functionalcharacterizationof pages 26-32, dine2022functionalcharacterizationof pages 68-70)
During Immune Responses:
- Spätzle-processing enzyme (SPE): The primary terminal protease activated by pathogen recognition cascades (nakano2023damagesensingmediated pages 5-6, dine2022functionalcharacterizationof pages 26-32, shan2023anevolutionarilyconserved pages 6-8)
- MP1 (Melanization Protease 1): Can cleave pro-Spaetzle and may function redundantly with SPE (nakano2023damagesensingmediated pages 5-6, shan2023anevolutionarilyconserved pages 6-8)
- Sp7 and Ser7: Additional serine proteases capable of processing pro-Spaetzle (shan2023anevolutionarilyconserved pages 6-8)
During Tissue Damage:
- Hayan and Persephone (Psh): Upstream serine proteases that can activate pro-Spaetzle in response to sterile tissue damage and reactive oxygen species (nakano2023damagesensingmediated pages 5-6, nakano2023damagesensingmediated pages 2-3, nakano2023damagesensingmediated pages 15-16, nakano2023damagesensingmediated pages 6-9)
Recent biochemical reconstitution studies from 2023 demonstrated that multiple proteases can act in an integrated network to generate active Spaetzle, with Grass, Psh, Hayan, and other components forming cascade pathways that respond to different microbial patterns and virulence factors (shan2023anevolutionarilyconserved pages 6-8).
The mature, cleaved Spaetzle C-106 domain binds to the extracellular portion of Toll receptors, specifically engaging the concave leucine-rich repeat (LRR) surface of the Toll ectodomain (saucereau2021structureanddynamics pages 1-3, saucereau2022structureanddynamics pages 1-2, saucereau2021structureanddynamics pages 3-5).
Structural studies from 2021-2022 using cryo-electron microscopy have revealed the molecular details of Spaetzle-Toll interactions (saucereau2021structureanddynamics pages 1-3, gangloff2021structureanddynamics pages 1-5, saucereau2022structureanddynamics pages 1-2, saucereau2021structureanddynamics pages 3-5):
Spaetzle binding induces critical conformational changes in Toll receptors (saucereau2021structureanddynamics pages 1-3, gangloff2021structureanddynamics pages 1-5, saucereau2022structureanddynamics pages 1-2):
Activated Toll receptors initiate a conserved intracellular signaling cascade that leads to antimicrobial peptide production and other immune responses (lima2021evolutionoftoll pages 1-2, dine2022functionalcharacterizationof pages 32-37, chowdhury2019tollfamilymembers pages 1-2):
| Pathway Component | Type | Function/Role | Location |
|---|---|---|---|
| Pro-Spätzle (Spz; P48607) | Inactive cytokine precursor | Secreted, disulfide-linked precursor containing an inhibitory prodomain and C-terminal cystine-knot signaling domain; it is not an enzyme or direct microbial sensor. (saucereau2022structureanddynamics pages 1-2, dine2022functionalcharacterizationof pages 26-32) | Secretory pathway → extracellular space/hemolymph or embryonic perivitelline space |
| Spätzle-processing enzyme (SPE) / Easter | Serine protease | SPE cleaves pro-Spätzle during immune responses; Easter performs the corresponding terminal cleavage during embryonic dorsoventral patterning. Cleavage exposes the active C-terminal C-106 ligand. (nakano2023damagesensingmediated pages 5-6, dine2022functionalcharacterizationof pages 26-32, shan2023anevolutionarilyconserved pages 6-8) | Extracellular protease cascade |
| Mature Spätzle C-106 | Cytokine-like ligand | Disulfide-stabilized cystine-knot dimer that binds the Toll ectodomain and rearranges Toll receptors so their juxtamembrane and intracellular signaling regions approach one another. (saucereau2022structureanddynamics pages 1-2, dine2022functionalcharacterizationof pages 26-32) | Extracellular |
| Toll (Toll-1) | Transmembrane receptor | Recognizes processed Spätzle through its extracellular leucine-rich-repeat domain; ligand-induced receptor reorganization activates the intracellular TIR domain. (saucereau2021structureanddynamics pages 3-5, kato2023analysisofthe pages 1-2) | Plasma membrane |
| MyD88 | Adaptor | Associates with the activated Toll TIR domain and nucleates the downstream death-domain signaling complex. (lima2021evolutionoftoll pages 1-2, dine2022functionalcharacterizationof pages 26-32) | Cytoplasmic face of plasma membrane |
| Tube | Scaffold/adaptor | Bridges MyD88 to Pelle through death-domain interactions, organizing the receptor-proximal signaling complex. (lima2021evolutionoftoll pages 1-2, dine2022functionalcharacterizationof pages 32-37) | Cytoplasmic |
| Pelle | Serine/threonine kinase | Functions in the MyD88–Tube–Pelle complex and promotes phosphorylation and subsequent removal of the NF-κB inhibitor Cactus. (lima2021evolutionoftoll pages 1-2, dine2022functionalcharacterizationof pages 32-37) | Cytoplasmic |
| Pellino | Positive signaling regulator | Positively regulates Pelle and supports propagation of Toll signaling. (lima2021evolutionoftoll pages 1-2) | Cytoplasmic |
| Cactus | IκB-like inhibitor | Retains Dorsal and Dif in the cytoplasm under resting conditions; Toll signaling promotes its phosphorylation, ubiquitylation, and proteasomal degradation. (lima2021evolutionoftoll pages 1-2, dine2022functionalcharacterizationof pages 32-37) | Cytoplasmic |
| Dorsal | NF-κB-family transcription factor | After Cactus removal, enters nuclei; generates the graded transcriptional response used in embryonic dorsoventral patterning and also contributes to larval immune responses. (rahimi2021thedynamicsand pages 43-46, pechmann2021strikingparallelsbetween pages 16-18, dine2022functionalcharacterizationof pages 32-37) | Cytoplasmic when inhibited → nuclear when activated |
| Dif | NF-κB-family transcription factor | Translocates to nuclei after Cactus degradation and is a principal Toll-pathway transcription factor in adult systemic immunity. (dine2022functionalcharacterizationof pages 32-37, chowdhury2019tollfamilymembers pages 1-2) | Cytoplasmic when inhibited → nuclear when activated |
| Drosomycin | Antimicrobial-peptide target gene/effector | Canonical Toll-responsive antifungal peptide gene induced by Dorsal/Dif-dependent transcription. (lima2021evolutionoftoll pages 1-2, chowdhury2019tollfamilymembers pages 1-2) | Transcribed in nucleus; peptide secreted extracellularly |
| Other Toll-responsive AMP genes | Target genes/effectors | Encode additional antimicrobial effectors; their induction links extracellular Spätzle activation to systemic host defense, although the exact AMP repertoire varies by tissue and context. (kato2023analysisofthe pages 1-2, chowdhury2019tollfamilymembers pages 1-2) | Transcribed in nucleus; peptide products generally secreted extracellularly |
Table: This table traces canonical signaling from extracellular pro-Spätzle processing through Toll, the MyD88–Tube–Pelle complex, Cactus removal, NF-κB activation, and antimicrobial-peptide expression. It also distinguishes the developmental and immune processing enzymes and locations of each step.
Key Signaling Components:
Transcriptional Targets:
The pathway culminates in expression of antimicrobial peptide genes, with drosomycin being the best-characterized Toll-responsive antifungal peptide (lima2021evolutionoftoll pages 1-2, chowdhury2019tollfamilymembers pages 1-2, kato2023analysisofthe pages 1-2). Additional targets include cecropins and other AMPs, with the specific repertoire varying by tissue and developmental context (kato2023analysisofthe pages 1-2, chowdhury2019tollfamilymembers pages 1-2, saucereau2021structureanddynamics pages 7-9).
Spaetzle is a secreted, extracellular protein that functions outside cells (bae2021tenebriomolitorspätzle pages 5-8, miao2024identificationofimmunityrelated pages 8-9, jang2021tmspzlikeplaysa pages 2-4, edosa2020tmspz6isessential pages 8-11):
Expression patterns vary by developmental stage and context (bae2021tenebriomolitorspätzle pages 5-8, liu2023serpin1aandserpin6 pages 4-5, edosa2020tmspz6isessential pages 8-11, edosa2020tmspz6isessential pages 11-13):
Spaetzle participates in multiple critical biological processes, with two major canonical roles and several emerging non-immune functions.
Spaetzle is essential for establishing the dorsoventral axis of the early Drosophila embryo (rahimi2021thedynamicsand pages 43-46, rahimi2021thedynamicsand pages 4-8, pechmann2021strikingparallelsbetween pages 16-18, rahimi2021thedynamicsand pages 37-40, pechmann2021strikingparallelsbetween pages 24-26):
Spaetzle is the key extracellular signal linking pathogen recognition to antimicrobial defense (dine2022functionalcharacterizationof pages 22-26, miao2024identificationofimmunityrelated pages 13-14, kato2023analysisofthe pages 1-2, dine2022functionalcharacterizationof pages 26-32):
Pathogen Specificity:
- The Spaetzle-Toll pathway responds primarily to Gram-positive bacteria and fungi (dine2022functionalcharacterizationof pages 22-26, kato2023analysisofthe pages 1-2, dine2022functionalcharacterizationof pages 26-32)
- Lys-type peptidoglycan from Gram-positive bacteria is recognized by PGRP-SA and GNBP1 (dine2022functionalcharacterizationof pages 22-26, miao2024identificationofimmunityrelated pages 13-14, kato2023analysisofthe pages 1-2)
- β-1,3-glucans from fungi are recognized by GNBP3 (dine2022functionalcharacterizationof pages 22-26, kato2023analysisofthe pages 1-2)
- Gram-negative bacteria can also activate the pathway, though typically more weakly than Gram-positive bacteria (miao2024identificationofimmunityrelated pages 13-14, edosa2020tmspz6isessential pages 11-13)
Immune Cascade:
1. Pathogen-associated molecular patterns trigger serine protease cascades
2. Terminal proteases (primarily SPE) cleave pro-Spaetzle to generate active ligand (dine2022functionalcharacterizationof pages 22-26, dine2022functionalcharacterizationof pages 26-32)
3. Active Spaetzle binds Toll receptors on hemocytes and fat body cells (dine2022functionalcharacterizationof pages 26-32, edosa2020tmspz6isessential pages 13-14)
4. Downstream signaling induces antimicrobial peptide genes, particularly the antifungal drosomycin (dine2022functionalcharacterizationof pages 22-26, dine2022functionalcharacterizationof pages 26-32, nakano2023damagesensingmediated pages 30-31)
Recent studies have revealed additional functions beyond classical immunity and development:
Tissue Damage Sensing and Sterile Inflammation:
A landmark 2023 study demonstrated that Spaetzle mediates responses to sterile tissue damage and apoptosis deficiency (nakano2023damagesensingmediated pages 2-3, nakano2023damagesensingmediated pages 15-16, nakano2023damagesensingmediated pages 6-9):
- Tissue damage and reactive oxygen species (ROS) activate Hayan and Persephone proteases (nakano2023damagesensingmediated pages 2-3, nakano2023damagesensingmediated pages 6-9)
- These proteases cleave pro-Spaetzle, triggering Toll pathway activation without infection (nakano2023damagesensingmediated pages 2-3, nakano2023damagesensingmediated pages 6-9)
- Genetically engineered uncleavable Spaetzle mutants confirmed that proteolytic activation is required for damage-induced Toll signaling (nakano2023damagesensingmediated pages 2-3, nakano2023damagesensingmediated pages 6-9)
- This damage-sensing mechanism contributes to tissue homeostasis and surveillance (nakano2023damagesensingmediated pages 2-3, nakano2023damagesensingmediated pages 6-9)
Stress-Induced Neurodegeneration:
A 2025 preprint reported that chronic stress activates Spaetzle-Toll-1 signaling in neurons, leading to neurodegeneration through glial phagocytosis (osaka2025aninnateimmune pages 13-17):
- Chronic light stress and mitochondrial dysfunction promote Spaetzle processing (osaka2025aninnateimmune pages 13-17)
- Toll-1 activation in stressed neurons induces expression of the glial phagocytic receptor Draper (osaka2025aninnateimmune pages 13-17)
- Excessive glial phagocytosis removes viable neurons, contributing to neurodegeneration (osaka2025aninnateimmune pages 13-17)
- This represents a novel non-cell-autonomous mechanism linking cellular stress to tissue degeneration (osaka2025aninnateimmune pages 13-17)
Drosophila melanogaster possesses six Spaetzle genes (Spz1-7, with Spz3/4 sometimes grouped), indicating functional diversification through gene duplication (dine2022functionalcharacterizationof pages 26-32, lima2021evolutionoftoll pages 14-15, lima2021evolutionoftoll pages 5-7):
The paralogs show receptor promiscuity, with some ligands capable of activating multiple Toll family members, though the physiological significance of many interactions remains to be fully elucidated (chowdhury2019tollfamilymembers pages 1-2, dine2022functionalcharacterizationof pages 26-32, gangloff2021structureanddynamics pages 9-11).
| Functional characteristic | Evidence-based annotation for Drosophila melanogaster Spätzle (spz; UniProt P48607) |
|---|---|
| Protein type / classification | Secreted, cytokine-like signaling protein and canonical extracellular ligand of Toll-1; it is not an enzyme and has no catalytic reaction or substrate specificity. It belongs functionally to the Spätzle family of cystine-knot Toll ligands (saucereau2021structureanddynamics pages 1-3, saucereau2022structureanddynamics pages 1-2, dine2022functionalcharacterizationof pages 26-32). |
| Primary molecular function | After proteolytic activation, the mature C-terminal ligand binds the extracellular leucine-rich-repeat region of Toll-1 and induces receptor rearrangement or oligomerization, bringing the receptor’s juxtamembrane and intracellular signaling regions into proximity (saucereau2021structureanddynamics pages 1-3, saucereau2021structureanddynamics pages 3-5, dine2022functionalcharacterizationof pages 26-32). |
| Structural features and domains | Synthesized as a precursor containing an N-terminal signal peptide, an inhibitory/regulatory prodomain, and a C-terminal approximately 106-residue C-106 signaling domain. C-106 adopts a disulfide-stabilized cystine-knot fold related to neurotrophin folds and forms the active dimeric ligand. These features agree with the Cystine-knot cytokine, Spaetzle, Spz/Toll-ligand-like, and PF16077 annotations supplied for P48607 (saucereau2021structureanddynamics pages 1-3, saucereau2022structureanddynamics pages 1-2, dine2022functionalcharacterizationof pages 26-32). |
| Biosynthesis and processing | The signal peptide directs the nascent protein into the secretory pathway. Secreted pro-Spätzle remains inactive because its prodomain masks receptor-binding determinants. Cleavage at the prodomain–C-106 junction generates the mature C-terminal signaling fragment; the prodomain and C-106 can remain associated noncovalently after cleavage (saucereau2022structureanddynamics pages 1-2, dine2022functionalcharacterizationof pages 26-32). |
| Activation mechanism | Context-specific extracellular serine-protease cascades activate pro-Spätzle. Easter is the principal terminal processing protease during embryonic dorsoventral patterning, whereas Spätzle-processing enzyme (SPE) is the principal immune terminal protease. Recent biochemical and genetic studies also support partially redundant processing by MP1, Sp7, Ser7, Grass, Hayan, or Persephone-dependent routes under infection or sterile-damage conditions (nakano2023damagesensingmediated pages 5-6, shan2023anevolutionarilyconserved pages 6-8). |
| Binding partners / receptors | The best-established physiological receptor is Toll-1. Mature C-106, rather than uncleaved pro-Spätzle, binds Toll’s extracellular domain. Cell-based studies also report that Spz can engage Toll-7, but these broader receptor interactions are less firmly established physiologically than the canonical Spz–Toll-1 pair and should not be conflated with activities of paralogs such as Spz5 (dine2022functionalcharacterizationof pages 26-32, chowdhury2019tollfamilymembers pages 1-2). |
| Subcellular localization | A soluble, secreted extracellular ligand—not an integral membrane protein. During embryogenesis, pro-Spätzle and activated Spätzle act in the perivitelline space surrounding the embryo. During systemic immunity, processing and receptor engagement occur in extracellular compartments associated with the hemolymph and immune-responsive tissues; local extracellular activation also occurs in the wing-disc lumen during cell competition (pechmann2021strikingparallelsbetween pages 16-18, rahimi2021thedynamicsand pages 37-40, alpar2018spatiallyrestrictedregulation pages 5-6). |
| Expression pattern | Maternal Spätzle supplies the early embryo, where spatially restricted activation, rather than simply localized synthesis, generates the dorsoventral signal. In postembryonic contexts, spz is expressed in immune and epithelial tissues and can participate in systemic or locally restricted Toll signaling. Tissue-expression claims from other insects cannot be transferred directly to D. melanogaster (rahimi2021thedynamicsand pages 43-46, pechmann2021strikingparallelsbetween pages 16-18, alpar2018spatiallyrestrictedregulation pages 5-6). |
| Key biological processes | Embryonic patterning: ventrally restricted cleavage generates an active-Spätzle gradient that activates Toll and establishes graded nuclear Dorsal, specifying dorsoventral cell fates. Innate immunity: pathogen-recognition and virulence-sensing protease cascades activate Spätzle, leading through Toll–MyD88–Tube–Pelle to Cactus removal, nuclear Dorsal/Dif, and antimicrobial genes such as drosomycin. Sterile tissue surveillance: cleavage-dependent Spätzle signaling responds to injury, ROS, apoptosis deficiency, and cell competition (dine2022functionalcharacterizationof pages 22-26, rahimi2021thedynamicsand pages 43-46, lima2021evolutionoftoll pages 1-2, nakano2023damagesensingmediated pages 2-3, nakano2023damagesensingmediated pages 6-9). |
Table: This table consolidates the molecular identity, structure, activation, localization, receptor interactions, and principal biological functions of Drosophila Spätzle (P48607). It distinguishes evidence specific to canonical spz from findings involving other Spätzle paralogs or insect species.
Spaetzle (spz, UniProt P48607) is a secreted, cytokine-like signaling protein—not an enzyme—that serves as the canonical activating ligand for Toll receptors in Drosophila melanogaster. Its primary molecular function is to bind Toll receptor ectodomains and induce conformational changes that enable downstream signaling. The protein is synthesized as an inactive precursor with an N-terminal signal peptide, regulatory prodomain, and C-terminal C-106 cystine-knot signaling domain. Context-specific serine protease cascades activate pro-Spaetzle by proteolytic cleavage, generating a mature disulfide-linked homodimer.
Functionally, Spaetzle operates in two major canonical contexts: (1) establishing the embryonic dorsoventral axis through spatially restricted activation and gradient formation, and (2) mediating innate immune responses to Gram-positive bacteria and fungi through activation of antimicrobial peptide transcription. The pathway proceeds through Toll→MyD88→Tube→Pelle→Cactus degradation→Dorsal/Dif nuclear translocation→antimicrobial gene expression.
Recent research (2023-2025) has expanded understanding of Spaetzle beyond immunity and development, revealing roles in tissue damage sensing, sterile inflammation, stress responses, and neurodegeneration. These findings establish Spaetzle as a versatile signaling molecule that integrates diverse inputs—pathogen recognition, tissue damage, oxidative stress—to coordinate cellular and organismal responses. The existence of six Spaetzle paralogues further suggests functional specialization, though the full scope of their distinct biological roles remains an active area of investigation.
References
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(gangloff2021structureanddynamics pages 1-5): Monique Gangloff, Yoann Saucereau, Thomas Wilson, Matthew Tang, Martin Moncrieffe, Steven Hardwick, Dimitri Chirgadze, Sandro Soares, Maria Marcaida, and Nicholas J. Gay. Structure and dynamics of pathway activation by the toll immunoreceptor from the viral mosquito vector aedes aegypti. ArXiv, Dec 2021. URL: https://doi.org/10.21203/rs.3.rs-1082903/v1, doi:10.21203/rs.3.rs-1082903/v1. This article has 0 citations.
(gangloff2021structureanddynamics pages 7-9): Monique Gangloff, Yoann Saucereau, Thomas Wilson, Matthew Tang, Martin Moncrieffe, Steven Hardwick, Dimitri Chirgadze, Sandro Soares, Maria Marcaida, and Nicholas J. Gay. Structure and dynamics of pathway activation by the toll immunoreceptor from the viral mosquito vector aedes aegypti. ArXiv, Dec 2021. URL: https://doi.org/10.21203/rs.3.rs-1082903/v1, doi:10.21203/rs.3.rs-1082903/v1. This article has 0 citations.
(lima2021evolutionoftoll pages 1-2): Letícia Ferreira Lima, André Quintanilha Torres, Rodrigo Jardim, Rafael Dias Mesquita, and Renata Schama. Evolution of toll, spatzle and myd88 in insects: the problem of the diptera bias. BMC Genomics, Jul 2021. URL: https://doi.org/10.1186/s12864-021-07886-7, doi:10.1186/s12864-021-07886-7. This article has 39 citations and is from a peer-reviewed journal.
(dine2022functionalcharacterizationof pages 32-37): H Zein El Dine. Functional characterization of anopheles gambiae spätzle gene family. Unknown journal, 2022.
(chowdhury2019tollfamilymembers pages 1-2): Munmun Chowdhury, Chun-Feng Li, Chun-Feng Li, Zhen He, Zhen He, Yuzhen Lu, Xu-Sheng Liu, Yufeng Wang, Y. Ip, M. Strand, Xiao-Qiang Yu, Xiao-Qiang Yu, and Xiao-Qiang Yu. Toll family members bind multiple spätzle proteins and activate antimicrobial peptide gene expression in drosophila. Journal of Biological Chemistry, 294:10172-10181, Jun 2019. URL: https://doi.org/10.1074/jbc.ra118.006804, doi:10.1074/jbc.ra118.006804. This article has 110 citations and is from a domain leading peer-reviewed journal.
(rahimi2021thedynamicsand pages 43-46): Neta Rahimi. The dynamics and precision of the spz/toll pathway in the drosophila embryo. Text, Jan 2021. URL: https://doi.org/10.34933/wis.000501, doi:10.34933/wis.000501. This article has 0 citations and is from a peer-reviewed journal.
(pechmann2021strikingparallelsbetween pages 16-18): Matthias Pechmann, Nathan James Kenny, Laura Pott, Peter Heger, Yen-Ta Chen, Thomas Buchta, Orhan Özüak, Jeremy Lynch, and Siegfried Roth. Striking parallels between dorsoventral patterning in drosophila and gryllus reveal a complex evolutionary history behind a model gene regulatory network. eLife, Mar 2021. URL: https://doi.org/10.7554/elife.68287, doi:10.7554/elife.68287. This article has 42 citations and is from a domain leading peer-reviewed journal.
(saucereau2021structureanddynamics pages 7-9): Yoann Saucereau, Tom H. Wilson, Matthew C. K. Tang, Martin C. Moncrieffe, Steven W. Hardwick, Dimitri Y. Chirgadze, Sandro G. Soares, Maria Jose Marcaida, Nick Gay, and Monique Gangloff. Structure and dynamics of toll immunoreceptor activation in the mosquito aedes aegypti. BioRxiv, Sep 2021. URL: https://doi.org/10.1101/2021.09.06.459066, doi:10.1101/2021.09.06.459066. This article has 0 citations.
(bae2021tenebriomolitorspätzle pages 5-8): Young Min Bae, Yong Hun Jo, Bharat Bhusan Patnaik, Bo Bae Kim, Ki Beom Park, Tariku Tesfaye Edosa, Maryam Keshavarz, Maryam Ali Mohammadie Kojour, Yong Seok Lee, and Yeon Soo Han. Tenebrio molitor spätzle 1b is required to confer antibacterial defense against gram-negative bacteria by regulation of antimicrobial peptides. Frontiers in Physiology, Nov 2021. URL: https://doi.org/10.3389/fphys.2021.758859, doi:10.3389/fphys.2021.758859. This article has 17 citations.
(jang2021tmspzlikeplaysa pages 2-4): H. Jang, B. Patnaik, Maryam Ali Mohammadie Kojour, Bo Bae Kim, Y. Bae, K. Park, Y. S. Lee, Hun-Jo Yong, and Ye-On-Soo Han. Tmspz-like plays a fundamental role in response to e. coli but not s. aureus or c. albican infection in tenebrio molitor via regulation of antimicrobial peptide production. International Journal of Molecular Sciences, 22:10888, Oct 2021. URL: https://doi.org/10.3390/ijms221910888, doi:10.3390/ijms221910888. This article has 25 citations.
(edosa2020tmspz6isessential pages 8-11): Tariku Tesfaye Edosa, Yong Hun Jo, Maryam Keshavarz, Young Min Bae, Dong Hyun Kim, Yong Seok Lee, and Yeon Soo Han. Tmspz6 is essential for regulating the immune response to escherichia coli and staphylococcus aureus infection in tenebrio molitor. Insects, 11:105, Feb 2020. URL: https://doi.org/10.3390/insects11020105, doi:10.3390/insects11020105. This article has 40 citations.
(rahimi2021thedynamicsand pages 37-40): Neta Rahimi. The dynamics and precision of the spz/toll pathway in the drosophila embryo. Text, Jan 2021. URL: https://doi.org/10.34933/wis.000501, doi:10.34933/wis.000501. This article has 0 citations and is from a peer-reviewed journal.
(edosa2020tmspz6isessential pages 11-13): Tariku Tesfaye Edosa, Yong Hun Jo, Maryam Keshavarz, Young Min Bae, Dong Hyun Kim, Yong Seok Lee, and Yeon Soo Han. Tmspz6 is essential for regulating the immune response to escherichia coli and staphylococcus aureus infection in tenebrio molitor. Insects, 11:105, Feb 2020. URL: https://doi.org/10.3390/insects11020105, doi:10.3390/insects11020105. This article has 40 citations.
(alpar2018spatiallyrestrictedregulation pages 5-6): Lale Alpar, Cora Bergantiños, and Laura A. Johnston. Spatially restricted regulation of spätzle/toll signaling during cell competition. Developmental cell, 46 6:706-719.e5, Sep 2018. URL: https://doi.org/10.1016/j.devcel.2018.08.001, doi:10.1016/j.devcel.2018.08.001. This article has 107 citations and is from a highest quality peer-reviewed journal.
(liu2023serpin1aandserpin6 pages 4-5): Huawei Liu, Jiahui Xu, Luoling Wang, Pengchao Guo, Zhangchen Tang, Xiaotong Sun, Xin Tang, Wei Wang, Lingyan Wang, Yang Cao, Qingyou Xia, and Ping Zhao. Serpin-1a and serpin-6 regulate the toll pathway immune homeostasis by synergistically inhibiting the spätzle-processing enzyme clip2 in silkworm, bombyx mori. PLOS Pathogens, 19:e1011740, Oct 2023. URL: https://doi.org/10.1371/journal.ppat.1011740, doi:10.1371/journal.ppat.1011740. This article has 32 citations and is from a highest quality peer-reviewed journal.
(rahimi2021thedynamicsand pages 4-8): Neta Rahimi. The dynamics and precision of the spz/toll pathway in the drosophila embryo. Text, Jan 2021. URL: https://doi.org/10.34933/wis.000501, doi:10.34933/wis.000501. This article has 0 citations and is from a peer-reviewed journal.
(pechmann2021strikingparallelsbetween pages 24-26): Matthias Pechmann, Nathan James Kenny, Laura Pott, Peter Heger, Yen-Ta Chen, Thomas Buchta, Orhan Özüak, Jeremy Lynch, and Siegfried Roth. Striking parallels between dorsoventral patterning in drosophila and gryllus reveal a complex evolutionary history behind a model gene regulatory network. eLife, Mar 2021. URL: https://doi.org/10.7554/elife.68287, doi:10.7554/elife.68287. This article has 42 citations and is from a domain leading peer-reviewed journal.
(dine2022functionalcharacterizationof pages 22-26): H Zein El Dine. Functional characterization of anopheles gambiae spätzle gene family. Unknown journal, 2022.
(miao2024identificationofimmunityrelated pages 13-14): Zelong Miao, Chao Xiong, Yang Wang, Tisheng Shan, and Haobo Jiang. Identification of immunity-related genes distinctly regulated by manduca sexta spӓtzle-1/2 and escherichia coli peptidoglycan. Insect Biochemistry and Molecular Biology, 168:104108, May 2024. URL: https://doi.org/10.1016/j.ibmb.2024.104108, doi:10.1016/j.ibmb.2024.104108. This article has 6 citations and is from a peer-reviewed journal.
(edosa2020tmspz6isessential pages 13-14): Tariku Tesfaye Edosa, Yong Hun Jo, Maryam Keshavarz, Young Min Bae, Dong Hyun Kim, Yong Seok Lee, and Yeon Soo Han. Tmspz6 is essential for regulating the immune response to escherichia coli and staphylococcus aureus infection in tenebrio molitor. Insects, 11:105, Feb 2020. URL: https://doi.org/10.3390/insects11020105, doi:10.3390/insects11020105. This article has 40 citations.
(nakano2023damagesensingmediated pages 30-31): Shotaro Nakano, Soshiro Kashio, Kei Nishimura, Asuka Takeishi, Hina Kosakamoto, Fumiaki Obata, Erina Kuranaga, Takahiro Chihara, Yoshio Yamauchi, Toshiaki Isobe, and Masayuki Miura. Damage sensing mediated by serine proteases hayan and persephone for toll pathway activation in apoptosis-deficient flies. PLOS Genetics, 19:e1010761, Jun 2023. URL: https://doi.org/10.1371/journal.pgen.1010761, doi:10.1371/journal.pgen.1010761. This article has 10 citations and is from a domain leading peer-reviewed journal.
(osaka2025aninnateimmune pages 13-17): Jiro Osaka, Toshiharu Ichinose, Mai Kanno, Satoko Hakeda-Suzuki, Takashi Suzuki, and Atsushi Sugie. An innate immune receptor toll-1 converts chronic light stress into glial-phagocytosis. bioRxiv, May 2026. URL: https://doi.org/10.1101/2025.09.03.673940, doi:10.1101/2025.09.03.673940. This article has 1 citations.
(lima2021evolutionoftoll pages 14-15): Letícia Ferreira Lima, André Quintanilha Torres, Rodrigo Jardim, Rafael Dias Mesquita, and Renata Schama. Evolution of toll, spatzle and myd88 in insects: the problem of the diptera bias. BMC Genomics, Jul 2021. URL: https://doi.org/10.1186/s12864-021-07886-7, doi:10.1186/s12864-021-07886-7. This article has 39 citations and is from a peer-reviewed journal.
(lima2021evolutionoftoll pages 5-7): Letícia Ferreira Lima, André Quintanilha Torres, Rodrigo Jardim, Rafael Dias Mesquita, and Renata Schama. Evolution of toll, spatzle and myd88 in insects: the problem of the diptera bias. BMC Genomics, Jul 2021. URL: https://doi.org/10.1186/s12864-021-07886-7, doi:10.1186/s12864-021-07886-7. This article has 39 citations and is from a peer-reviewed journal.
(gangloff2021structureanddynamics pages 9-11): Monique Gangloff, Yoann Saucereau, Thomas Wilson, Matthew Tang, Martin Moncrieffe, Steven Hardwick, Dimitri Chirgadze, Sandro Soares, Maria Marcaida, and Nicholas J. Gay. Structure and dynamics of pathway activation by the toll immunoreceptor from the viral mosquito vector aedes aegypti. ArXiv, Dec 2021. URL: https://doi.org/10.21203/rs.3.rs-1082903/v1, doi:10.21203/rs.3.rs-1082903/v1. This article has 0 citations.