Pub Date : 2025-12-08DOI: 10.1016/j.ydbio.2025.12.005
Shih-Chi Li , Yu-Chi Lin , Chung-Der Hsiao , Shyh-Jye Lee
Neutrophils play essential roles in host defense, but the mechanisms governing their developmental distribution remain poorly understood. Here, we identify a previously unrecognized function of lysophosphatidic acid receptor 1 (Lpar1) in maintaining neutrophil retention during early zebrafish development. Contrary to its previously described pro-inflammatory role, Lpar1 acts in an anti-inflammatory manner by preventing premature neutrophil dispersal. Mechanistically, Lpar1 regulates the expression of cxcl12a in the caudal hematopoietic tissue (CHT), establishing a novel Lpar1–Cxcl12a signaling axis that governs neutrophil localization. Lpar1 also influences neutrophil mobility through its effects on vascular integrity in the CHT, which is severely disrupted in Lpar1 morphants but may be mildly affected in Lpar1 mutants. Dispersed neutrophils are predominantly recruited to the superficial epidermal layer, where numerous apoptotic cells are present. Collectively, these findings refine current models of immune regulation during development and reveal an alternative mechanism that may contribute to the development of inflammatory skin disorders.
{"title":"Stay or stray: Lpar1 regulates neutrophil retention and epidermal homeostasis in early zebrafish development","authors":"Shih-Chi Li , Yu-Chi Lin , Chung-Der Hsiao , Shyh-Jye Lee","doi":"10.1016/j.ydbio.2025.12.005","DOIUrl":"10.1016/j.ydbio.2025.12.005","url":null,"abstract":"<div><div>Neutrophils play essential roles in host defense, but the mechanisms governing their developmental distribution remain poorly understood. Here, we identify a previously unrecognized function of lysophosphatidic acid receptor 1 (Lpar1) in maintaining neutrophil retention during early zebrafish development. Contrary to its previously described pro-inflammatory role, Lpar1 acts in an anti-inflammatory manner by preventing premature neutrophil dispersal. Mechanistically, Lpar1 regulates the expression of <em>cxcl12a</em> in the caudal hematopoietic tissue (CHT), establishing a novel Lpar1–Cxcl12a signaling axis that governs neutrophil localization. Lpar1 also influences neutrophil mobility through its effects on vascular integrity in the CHT, which is severely disrupted in Lpar1 morphants but may be mildly affected in Lpar1 mutants. Dispersed neutrophils are predominantly recruited to the superficial epidermal layer, where numerous apoptotic cells are present. Collectively, these findings refine current models of immune regulation during development and reveal an alternative mechanism that may contribute to the development of inflammatory skin disorders.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 171-187"},"PeriodicalIF":2.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-06DOI: 10.1016/j.ydbio.2025.12.004
Miglė Kalvaitytė-Repečkė , Sofija Gabrilavičiūtė , Kotryna Kvederavičiūtė , Leonard Burg , Edita Bakūnaitė , Kenneth D. Poss , Darius Balciunas
Unlike mammals, zebrafish (Danio rerio) are able to regenerate their hearts after injury, making them an excellent model organism for studying the molecular mechanisms underlying heart regeneration. Epicardium, the outermost layer of the heart, is an essential player in this process. Injury-induced epicardium activation, characterized by the expression of embryonic epicardial marker genes including tcf21, supports cardiac regeneration by providing various cell types and releasing paracrine signals that promote the restoration of damaged tissue. However, the molecular mechanisms involved in this process are insufficiently understood. In this study, we describe a conditional tcf21flox allele and use it to investigate the role of Tcf21 in heart regeneration. By employing 4-hydroxytamoxifen inducible CreERT2 recombinase, we eliminated tcf21 expression in adult fish. Our findings indicate that loss of this transcription factor reduces the presence of dedifferentiated cardiomyocytes in the injury area and impairs heart regeneration. This work provides new insights into the molecular basis of the epicardial response to heart injury and its role in guiding heart regeneration.
{"title":"Epicardial Tcf21 facilitates cardiomyocyte dedifferentiation and heart regeneration in zebrafish","authors":"Miglė Kalvaitytė-Repečkė , Sofija Gabrilavičiūtė , Kotryna Kvederavičiūtė , Leonard Burg , Edita Bakūnaitė , Kenneth D. Poss , Darius Balciunas","doi":"10.1016/j.ydbio.2025.12.004","DOIUrl":"10.1016/j.ydbio.2025.12.004","url":null,"abstract":"<div><div>Unlike mammals, zebrafish (<em>Danio rerio</em>) are able to regenerate their hearts after injury, making them an excellent model organism for studying the molecular mechanisms underlying heart regeneration. Epicardium, the outermost layer of the heart, is an essential player in this process. Injury-induced epicardium activation, characterized by the expression of embryonic epicardial marker genes including <em>tcf21,</em> supports cardiac regeneration by providing various cell types and releasing paracrine signals that promote the restoration of damaged tissue. However, the molecular mechanisms involved in this process are insufficiently understood. In this study, we describe a conditional <em>tcf21</em><sup><em>flox</em></sup> allele and use it to investigate the role of Tcf21 in heart regeneration. By employing 4-hydroxytamoxifen inducible CreER<sup>T2</sup> recombinase, we eliminated <em>tcf21</em> expression in adult fish. Our findings indicate that loss of this transcription factor reduces the presence of dedifferentiated cardiomyocytes in the injury area and impairs heart regeneration. This work provides new insights into the molecular basis of the epicardial response to heart injury and its role in guiding heart regeneration.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"199"},"PeriodicalIF":2.1,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-05DOI: 10.1016/j.ydbio.2025.12.003
Daisy Xin , Mycah Sewell , Elli Emmanouil , Scott D. Weatherbee
Multiple congenital anomalies have been linked to defects in the formation or function of a small cellular organelle called the cilium. The severity of cilia-related syndromes (ciliopathies) ranges from viable with fertility defects to embryonic lethal, often with different mutations in the same gene resulting in highly variable phenotypes. While some of the disparity is likely due to differential effects of specific mutations, genetic variants at other loci could serve as ciliopathy modifiers. This could lead to the same mutation causing distinct effects in different individuals. Here, we show that a loss-of-function mutation in Ift56, a key gene involved in cilia protein trafficking, has dramatic phenotypic differences depending on the genetic background in mice. It has previously been reported that in the Balb/cByJ background, Ift56hop homozygous mutants are viable as adults, males are sterile, and homozygotes move their hindlimbs in tandem, resulting in a hopping gait. In contrast, we demonstrate that in the C57BL/6J background, Ift56hop homozygotes are perinatal lethal, and have multiple skeletal and organ defects, including the formation of tracheoesophageal fistulas. Using Single Nucleotide Polymorphisms (SNPs) that differ between these mouse strains, we show that a modifier of the Ift56hop phenotype maps to Chromosome 4. Mutations in IFT56 and other cilia-related genes are being discovered in a growing number of human patients so understanding the mechanisms of their pathology is critical. Our study highlights the use of mouse models to identify ciliopathy modifier loci, with direct implications for human diagnostics.
{"title":"Genetic background influences the extent and severity of cilia-related congenital anomalies in Ift56/Ttc26 mutant mice","authors":"Daisy Xin , Mycah Sewell , Elli Emmanouil , Scott D. Weatherbee","doi":"10.1016/j.ydbio.2025.12.003","DOIUrl":"10.1016/j.ydbio.2025.12.003","url":null,"abstract":"<div><div>Multiple congenital anomalies have been linked to defects in the formation or function of a small cellular organelle called the cilium. The severity of cilia-related syndromes (ciliopathies) ranges from viable with fertility defects to embryonic lethal, often with different mutations in the same gene resulting in highly variable phenotypes. While some of the disparity is likely due to differential effects of specific mutations, genetic variants at other loci could serve as ciliopathy modifiers. This could lead to the same mutation causing distinct effects in different individuals. Here, we show that a loss-of-function mutation in <em>Ift56</em>, a key gene involved in cilia protein trafficking, has dramatic phenotypic differences depending on the genetic background in mice. It has previously been reported that in the Balb/cByJ background, <em>Ift56</em><sup><em>hop</em></sup> homozygous mutants are viable as adults, males are sterile, and homozygotes move their hindlimbs in tandem, resulting in a hopping gait. In contrast, we demonstrate that in the C57BL/6J background, <em>Ift56</em><sup><em>hop</em></sup> homozygotes are perinatal lethal, and have multiple skeletal and organ defects, including the formation of tracheoesophageal fistulas. Using Single Nucleotide Polymorphisms (SNPs) that differ between these mouse strains, we show that a modifier of the <em>Ift56</em><sup><em>hop</em></sup> phenotype maps to Chromosome 4. Mutations in <em>IFT56</em> and other cilia-related genes are being discovered in a growing number of human patients so understanding the mechanisms of their pathology is critical. Our study highlights the use of mouse models to identify ciliopathy modifier loci, with direct implications for human diagnostics.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 138-147"},"PeriodicalIF":2.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.1016/j.ydbio.2025.12.002
Qootsvenma Denipah-Cook , Bryanna V. Saxton , Kristin B. Artinger , Lomeli C. Shull
Mandibular bone development depends on the formation of a cartilaginous anlage Meckel's cartilage derived from neural crest cells (NCC) and intramembranous ossification or direct differentiation of NCCs toward osteoblasts. Wnt/β-catenin signaling drives osteogenic vs chondrogenic differentiation and must be tightly controlled during the differentiation of osteochondroprogenitors. Chromatin remodelers add hierarchal regulation to the activation and repression of crucially timed gene regulatory networks and signaling cascades. In this study, we investigated the function of two chromatin remodelers—histone methyltransferases, PRDM3 and PRDM16 during murine craniofacial development. Conditionally ablating both Prdm3 and Prdm16 in the neural crest lineage using the Wnt1-Cre driver resulted in dramatic craniofacial phenotypes, including a severely hypoplastic mandible with complete absence of Meckel's cartilage at E18.5. Focusing on the Meckel's cartilage and mandibular bone phenotype, histological analysis demonstrated a significant increase in RUNX2+ osteoblast precursors, and loss of SOX9+ chondrogenic cells, suggesting an increase in osteoblast progenitors at the expense of chondrocytes that would otherwise form the Meckel's cartilage. This was not due to alterations in proliferation or apoptosis, as we observed no significant changes in the number of phosphoH3+ or cleaved caspase3+ cells in the mandibular process at E11.5, suggesting lack of NCC-derived chondrocytes is due to a change in NCC osteochondroprogenitor fate decisions. mRNA transcripts and protein abundance of Wnt/β-catenin signaling components were elevated in the mandibular process during initial NCC osteochondroprogenitor condensation events, suggesting PRDM3 and PRDM16 normally restrict expression of Wnt/β-catenin signaling components during NCC-derived osteochondroprogenitor differentiation to promote chondrogenesis and Meckel's cartilage formation. Taken together, PRDM3 and PRDM16 are required for NCC differentiation toward chondrocytes during Meckel's cartilage formation by controlling proper spatiotemporal Wnt/β-catenin transcriptional activity and this process is necessary for morphogenesis of the developing mandible.
{"title":"PRDM paralogs are required for Meckel's cartilage formation during mandibular bone development","authors":"Qootsvenma Denipah-Cook , Bryanna V. Saxton , Kristin B. Artinger , Lomeli C. Shull","doi":"10.1016/j.ydbio.2025.12.002","DOIUrl":"10.1016/j.ydbio.2025.12.002","url":null,"abstract":"<div><div>Mandibular bone development depends on the formation of a cartilaginous anlage Meckel's cartilage derived from neural crest cells (NCC) and intramembranous ossification or direct differentiation of NCCs toward osteoblasts. Wnt/β-catenin signaling drives osteogenic vs chondrogenic differentiation and must be tightly controlled during the differentiation of osteochondroprogenitors. Chromatin remodelers add hierarchal regulation to the activation and repression of crucially timed gene regulatory networks and signaling cascades. In this study, we investigated the function of two chromatin remodelers—histone methyltransferases, PRDM3 and PRDM16 during murine craniofacial development. Conditionally ablating both <em>Prdm3</em> and <em>Prdm16</em> in the neural crest lineage using the Wnt1-Cre driver resulted in dramatic craniofacial phenotypes, including a severely hypoplastic mandible with complete absence of Meckel's cartilage at E18.5. Focusing on the Meckel's cartilage and mandibular bone phenotype, histological analysis demonstrated a significant increase in RUNX2+ osteoblast precursors, and loss of SOX9+ chondrogenic cells, suggesting an increase in osteoblast progenitors at the expense of chondrocytes that would otherwise form the Meckel's cartilage. This was not due to alterations in proliferation or apoptosis, as we observed no significant changes in the number of phosphoH3+ or cleaved caspase3+ cells in the mandibular process at E11.5, suggesting lack of NCC-derived chondrocytes is due to a change in NCC osteochondroprogenitor fate decisions. mRNA transcripts and protein abundance of Wnt/β-catenin signaling components were elevated in the mandibular process during initial NCC osteochondroprogenitor condensation events, suggesting PRDM3 and PRDM16 normally restrict expression of Wnt/β-catenin signaling components during NCC-derived osteochondroprogenitor differentiation to promote chondrogenesis and Meckel's cartilage formation. Taken together, PRDM3 and PRDM16 are required for NCC differentiation toward chondrocytes during Meckel's cartilage formation by controlling proper spatiotemporal Wnt/β-catenin transcriptional activity and this process is necessary for morphogenesis of the developing mandible.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 210-223"},"PeriodicalIF":2.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.1016/j.ydbio.2025.11.016
Keevon Flohr , Michael Janeček , Lingyun Wang , Vicente Valle , Shaohua Pi , Rui T. Peixoto , Susana da Silva
Human retinal organoids (hRetOrg) derived from human induced pluripotent stem cells (hiPSCs) have emerged as powerful in vitro systems for studying retinal development, modeling retinal diseases, and evaluating therapeutic strategies. However, current genetic manipulation approaches, such as stable hiPSC line generation and viral transduction, are laborious and costly, offering limited spatial specificity and high variability in transgene expression. Here, we report a rapid, scalable, and spatially precise electroporation-based platform for efficient plasmid-based gene delivery in early-stage hRetOrg. Our method enables tunable and region-specific transfection of retinal progenitor cells without viral vectors or clonal selection. When coupled with resonant-scanning two-photon microscopy, this approach allows fast live cell imaging of whole organoids with subcellular resolution. Taken together, our versatile system supports high-throughput genetic manipulation and imaging in intact hRetOrg, advancing studies of human retinal development, gene function, and disease pathophysiology.
{"title":"Electroporation-based gene delivery and whole-organoid imaging in human retinal organoids","authors":"Keevon Flohr , Michael Janeček , Lingyun Wang , Vicente Valle , Shaohua Pi , Rui T. Peixoto , Susana da Silva","doi":"10.1016/j.ydbio.2025.11.016","DOIUrl":"10.1016/j.ydbio.2025.11.016","url":null,"abstract":"<div><div>Human retinal organoids (hRetOrg) derived from human induced pluripotent stem cells (hiPSCs) have emerged as powerful <em>in vitro</em> systems for studying retinal development, modeling retinal diseases, and evaluating therapeutic strategies. However, current genetic manipulation approaches, such as stable hiPSC line generation and viral transduction, are laborious and costly, offering limited spatial specificity and high variability in transgene expression. Here, we report a rapid, scalable, and spatially precise electroporation-based platform for efficient plasmid-based gene delivery in early-stage hRetOrg. Our method enables tunable and region-specific transfection of retinal progenitor cells without viral vectors or clonal selection. When coupled with resonant-scanning two-photon microscopy, this approach allows fast live cell imaging of whole organoids with subcellular resolution. Taken together, our versatile system supports high-throughput genetic manipulation and imaging in intact hRetOrg, advancing studies of human retinal development, gene function, and disease pathophysiology.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 148-159"},"PeriodicalIF":2.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.ydbio.2025.12.001
Janina Kueper , Ivan Moskowitz , Rolf Stottmann , Irene Zohn , Mustafa K. Khokha
{"title":"Challenges and opportunities for understanding the genetic causes of congenital anomalies","authors":"Janina Kueper , Ivan Moskowitz , Rolf Stottmann , Irene Zohn , Mustafa K. Khokha","doi":"10.1016/j.ydbio.2025.12.001","DOIUrl":"10.1016/j.ydbio.2025.12.001","url":null,"abstract":"","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 160-170"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1016/S0012-1606(25)00329-X
{"title":"Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information","authors":"","doi":"10.1016/S0012-1606(25)00329-X","DOIUrl":"10.1016/S0012-1606(25)00329-X","url":null,"abstract":"","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Page OBC"},"PeriodicalIF":2.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-22DOI: 10.1016/j.ydbio.2025.11.012
Ben Dillon Cox , Hailong Yang , Joshua Moore , Neha Ahuja , Kirk Amundson , Nicole Aponte-Santiago , Cagney Coomer , Yan Gong , Amy L. Herbert , Concepcion Manzano , Jesús Martínez-Gómez , James Satterlee , Siobhán M. Brady , Crystal D. Rogers
Developmental biology stands at a crossroads. While some have suggested the field is in decline, we, early-career developmental biologists, see an era of renewal driven by conceptual expansion, technical innovation, and cross-disciplinary integration. In this Commentary, we reflect on discussions from a 2024 workshop of postdoctoral scholars from across North America, outlining shared challenges and opportunities that will shape the field's future. We argue that the perceived crisis in developmental biology stems not from a lack of relevance, but from a narrow definition that overlooks its broader reach, from embryogenesis to regeneration, stem cell biology, aging, and environmental responsiveness. We highlight how emerging model organisms, single-cell systems, and advances in imaging and genomics now enable comparative and mechanistic insights across the tree of life. To sustain this progress, we call for renewed investment in basic research, structural reforms to support early-career scientists, and accessible community-driven resources for emerging model systems. Finally, we emphasize the importance of public engagement, equitable mentorship, and acknowledgment of the field's complex history to foster an inclusive and resilient scientific community. Together, these efforts can reprogram the trajectory of developmental biology and secure its central place in understanding the origins and dynamics of life.
{"title":"Reprogramming our fate: a postdoctoral reflection on current challenges and prospects for developmental biology","authors":"Ben Dillon Cox , Hailong Yang , Joshua Moore , Neha Ahuja , Kirk Amundson , Nicole Aponte-Santiago , Cagney Coomer , Yan Gong , Amy L. Herbert , Concepcion Manzano , Jesús Martínez-Gómez , James Satterlee , Siobhán M. Brady , Crystal D. Rogers","doi":"10.1016/j.ydbio.2025.11.012","DOIUrl":"10.1016/j.ydbio.2025.11.012","url":null,"abstract":"<div><div>Developmental biology stands at a crossroads. While some have suggested the field is in decline, we, early-career developmental biologists, see an era of renewal driven by conceptual expansion, technical innovation, and cross-disciplinary integration. In this Commentary, we reflect on discussions from a 2024 workshop of postdoctoral scholars from across North America, outlining shared challenges and opportunities that will shape the field's future. We argue that the perceived crisis in developmental biology stems not from a lack of relevance, but from a narrow definition that overlooks its broader reach, from embryogenesis to regeneration, stem cell biology, aging, and environmental responsiveness. We highlight how emerging model organisms, single-cell systems, and advances in imaging and genomics now enable comparative and mechanistic insights across the tree of life. To sustain this progress, we call for renewed investment in basic research, structural reforms to support early-career scientists, and accessible community-driven resources for emerging model systems. Finally, we emphasize the importance of public engagement, equitable mentorship, and acknowledgment of the field's complex history to foster an inclusive and resilient scientific community. Together, these efforts can reprogram the trajectory of developmental biology and secure its central place in understanding the origins and dynamics of life.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 132-137"},"PeriodicalIF":2.1,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-21DOI: 10.1016/j.ydbio.2025.11.011
David Paulding , Simon J.Y. Han , Jonathan Timmons , Michelle Caye , Alexa Riedel , Samantha A. Brugmann , Lindsey Barske
Nuclear receptors are iteratively deployed during neural crest development, from pre-induction through differentiation stages. NR2F1 and NR2F2 in particular have been proposed as broad regulators of early neural crest gene expression in mammals, but the timing, extent, and redundancy of their developmental requirement has remained unclear, as Nr2f1 and Nr2f2 single mouse mutants present only minimal craniofacial phenotypes. Here we report the dynamic expression patterns of Nr2f1 and Nr2f2 in the mouse cranial neural crest from specification through post-migratory stages. Combined conditional knockout of both Nr2f1 and Nr2f2 in the neural crest with Wnt1-Cre or Pax3Cre caused severe midfacial clefting, loss of the maxilla and palate, and hypoplasticity of all other facial skeletal elements except the distal mandible. These perinatal phenotypes were rooted in a major shortage of pharyngeal arch mesenchyme at mid-gestation. This in turn traced to a deficiency of migrating neural crest cells, first evident in the trailing part of the first arch migratory stream at embryonic day 8.75. RNAseq at a slightly earlier stage revealed downregulation of many migratory neural crest genes, including a possible direct target, the phospholipase Plcg2. These findings reveal a vital requirement for NR2F1/2 within the later-forming cranial neural crest.
{"title":"Cranial neural crest shortage leads to extensive craniofacial anomalies in mice mutant for the NR2F1/2 nuclear receptors","authors":"David Paulding , Simon J.Y. Han , Jonathan Timmons , Michelle Caye , Alexa Riedel , Samantha A. Brugmann , Lindsey Barske","doi":"10.1016/j.ydbio.2025.11.011","DOIUrl":"10.1016/j.ydbio.2025.11.011","url":null,"abstract":"<div><div>Nuclear receptors are iteratively deployed during neural crest development, from pre-induction through differentiation stages. NR2F1 and NR2F2 in particular have been proposed as broad regulators of early neural crest gene expression in mammals, but the timing, extent, and redundancy of their developmental requirement has remained unclear, as <em>Nr2f1</em> and <em>Nr2f2</em> single mouse mutants present only minimal craniofacial phenotypes. Here we report the dynamic expression patterns of <em>Nr2f1</em> and <em>Nr2f2</em> in the mouse cranial neural crest from specification through post-migratory stages. Combined conditional knockout of both <em>Nr2f1</em> and <em>Nr2f2</em> in the neural crest with <em>Wnt1-</em>Cre or <em>Pax3</em><sup>Cre</sup> caused severe midfacial clefting, loss of the maxilla and palate, and hypoplasticity of all other facial skeletal elements except the distal mandible. These perinatal phenotypes were rooted in a major shortage of pharyngeal arch mesenchyme at mid-gestation. This in turn traced to a deficiency of migrating neural crest cells, first evident in the trailing part of the first arch migratory stream at embryonic day 8.75. RNAseq at a slightly earlier stage revealed downregulation of many migratory neural crest genes, including a possible direct target, the phospholipase <em>Plcg2</em>. These findings reveal a vital requirement for NR2F1/2 within the later-forming cranial neural crest.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 102-118"},"PeriodicalIF":2.1,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.1016/j.ydbio.2025.11.014
Nozomu M. Totsuka, Kohji Hotta
Metamorphosis is a key event in development that is conserved in many marine organisms. Ciona intestinalis type A induces metamorphosis through the settlement of papillae onto the substrate. The papilla consists of collocytes (CCs), primary sensory neurons (PSNs), and axial columnar cells (ACCs), but it remains unclear whether PSNs alone can induce metamorphosis. Manipulating single neurons is crucial for elucidating the neural network system that drives metamorphosis. In this study, we developed an optogenetic system in which ChrimsonR, a red-shifted mutant of channelrhodopsin, was expressed exclusively in PSNs, enabling metamorphosis to be induced by light stimulation. A Ciona-optimized self-cleaving peptide, T2A, was used to co-express the Ca2+ indicator GCaMP6s, allowing us to monitor neural activity during light stimulation. Activation of PSNs alone induced a series of metamorphic events, including epidermal backward movement, mesenchymal cell extravasation, and tail regression. Furthermore, we confirmed that metamorphosis proceeded to the juvenile stage. Metamorphosis was induced even with intermittent light stimulation, and the total stimulation time required for its initiation was approximately 6 min. The optogenetic system developed in this study may significantly contribute to elucidating the link between neuronal function and metamorphosis at the single-cell level.
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