Injury-induced Neuregulin-EGFR signaling from muscle mobilizes stem cells for whole-body regeneration in acoels.
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| Title: | Injury-induced Neuregulin-EGFR signaling from muscle mobilizes stem cells for whole-body regeneration in acoels. |
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| Authors: | Stevens B; Department of Molecular Biosciences, Northwestern University, Evanston, IL, 60208, USA., Popp R; Department of Molecular Biosciences, Northwestern University, Evanston, IL, 60208, USA., Valera H; Department of Molecular Biosciences, Northwestern University, Evanston, IL, 60208, USA., Krueger K; Department of Molecular Biosciences, Northwestern University, Evanston, IL, 60208, USA., Petersen CP; Department of Molecular Biosciences, Northwestern University, Evanston, IL, 60208, USA; Robert Lurie Comprehensive Cancer Center, Northwestern University, Evanston, IL, 60208, USA. Electronic address: christian-p-petersen@northwestern.edu. |
| Source: | Developmental biology [Dev Biol] 2025 Dec; Vol. 528, pp. 105-116. Date of Electronic Publication: 2025 Sep 06. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: United States NLM ID: 0372762 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-564X (Electronic) Linking ISSN: 00121606 NLM ISO Abbreviation: Dev Biol Subsets: MEDLINE |
| Imprint Name(s): | Publication: San Diego, CA : Elsevier Original Publication: New York. |
| MeSH Terms: | Regeneration*/physiology , Signal Transduction*/physiology , ErbB Receptors*/metabolism , ErbB Receptors*/genetics , Muscles*/metabolism , Stem Cells*/cytology , Stem Cells*/metabolism , Neuregulin-1*/metabolism , Neuregulin-1*/genetics , Neuregulins*/metabolism , Neuregulins*/genetics, Animals ; RNA Interference ; Cell Movement ; Wound Healing |
| Abstract: | Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. The activation of progenitor cells near wound sites is a common feature of regeneration across species, but the conserved signaling mechanisms responsible for this step in whole-body regeneration are still incompletely understood. The acoel Hofstenia miamia undergoes whole-body regeneration using Piwi + pluripotent adult stem cells (neoblasts) that accumulate at amputation sites early in regeneration. The EGFR signaling pathway has broad roles in controlling proliferation, migration, differentiation, and cell survival across metazoans. Using candidate RNAi screening, we identify the Hofstenia EGFR egfr-1 and Neuregulin nrg-1 genes as essential for blastema formation. Structure prediction of NRG-1 and EGFR-1 proteins suggests these factors interact directly. After amputation injuries, nrg-1 expression is induced in body-wall muscle cells at the wound site by 6 h and localizes to the tip of the outgrowing blastema by 24 h and sustains for several days, while egfr-1 is broadly expressed, including in muscle and neoblasts. The early phase of nrg-1 expression occurs at incision sites that repair through wound healing while the late phase is specific to blastema formation. Under nrg-1(RNAi) and egfr-1(RNAi) conditions that impair blastema formation, animals still undergo the earliest responses to injury to activate expression of the Early Growth Response transcription factor egr. In addition, RNAi of nrg-1 only after amputation results in regeneration failure, indicating regeneration requires new nrg-1 expression. nrg-1(RNAi) and egfr-1(RNAi) animals possess Piwi+ and H3P + mitotic neoblasts which hyperproliferate normally after amputation, but these cells fail to accumulate at the wound site. Therefore, muscle provides a source for Neuregulin-EGFR signaling after injury and is necessary for the mobilization of proliferative progenitors to enable blastema outgrowth for whole-body regeneration in Hofstenia. These results indicate a shared functional requirement for muscle signaling to enable regeneration between planarians and acoels across 550 million years of evolution. (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Comments: | Update of: bioRxiv. 2024 Dec 23:2024.12.23.630141. doi: 10.1101/2024.12.23.630141.. (PMID: 39764063) |
| Substance Nomenclature: | EC 2.7.10.1 (ErbB Receptors) 0 (Neuregulin-1) 0 (Neuregulins) |
| Entry Date(s): | Date Created: 20250908 Date Completed: 20251012 Latest Revision: 20251012 |
| Update Code: | 20251013 |
| DOI: | 10.1016/j.ydbio.2025.08.024 |
| PMID: | 40921377 |
| Database: | MEDLINE |
Nájsť tento článok vo Web of Science | Abstract: | Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.<br />The activation of progenitor cells near wound sites is a common feature of regeneration across species, but the conserved signaling mechanisms responsible for this step in whole-body regeneration are still incompletely understood. The acoel Hofstenia miamia undergoes whole-body regeneration using Piwi + pluripotent adult stem cells (neoblasts) that accumulate at amputation sites early in regeneration. The EGFR signaling pathway has broad roles in controlling proliferation, migration, differentiation, and cell survival across metazoans. Using candidate RNAi screening, we identify the Hofstenia EGFR egfr-1 and Neuregulin nrg-1 genes as essential for blastema formation. Structure prediction of NRG-1 and EGFR-1 proteins suggests these factors interact directly. After amputation injuries, nrg-1 expression is induced in body-wall muscle cells at the wound site by 6 h and localizes to the tip of the outgrowing blastema by 24 h and sustains for several days, while egfr-1 is broadly expressed, including in muscle and neoblasts. The early phase of nrg-1 expression occurs at incision sites that repair through wound healing while the late phase is specific to blastema formation. Under nrg-1(RNAi) and egfr-1(RNAi) conditions that impair blastema formation, animals still undergo the earliest responses to injury to activate expression of the Early Growth Response transcription factor egr. In addition, RNAi of nrg-1 only after amputation results in regeneration failure, indicating regeneration requires new nrg-1 expression. nrg-1(RNAi) and egfr-1(RNAi) animals possess Piwi+ and H3P + mitotic neoblasts which hyperproliferate normally after amputation, but these cells fail to accumulate at the wound site. Therefore, muscle provides a source for Neuregulin-EGFR signaling after injury and is necessary for the mobilization of proliferative progenitors to enable blastema outgrowth for whole-body regeneration in Hofstenia. These results indicate a shared functional requirement for muscle signaling to enable regeneration between planarians and acoels across 550 million years of evolution.<br /> (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.) |
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| ISSN: | 1095-564X |
| DOI: | 10.1016/j.ydbio.2025.08.024 |