Pub Date : 2025-10-06DOI: 10.1016/j.ydbio.2025.10.001
Aubrey M. Kent , Carlos Guerrero-Hernández , Carolyn Brewster , Sean McKinney , Jason A. Morrison , Mary C. McKinney , Eric J. Ross , Frederick G. Mann Jr. , Blair W. Benham-Pyle , Alejandro Sánchez Alvarado
Planarians exhibit extraordinary regenerative abilities driven by pluripotent neoblasts, yet the roles of post-mitotic progenitor and differentiated cells in this process remain incompletely understood. Here, we investigate the function of agat+ cells, epidermal progenitors expressing members of the arginine:glycine amidinotransferase (agat) gene family, in the regeneration of Schmidtea mediterranea. Comprehensive analysis of all five planarian agat paralogs revealed that agat-1, -2, -3, and -4 are co-expressed in subepidermal populations enriched at wound sites, while agat-5 is minimally expressed. RNAi-mediated knockdown of agat-1 and agat-2 resulted in severe defects: agat-1 primarily disrupted tissue homeostasis, whereas agat-2 specifically impaired blastema formation and stem cell maintenance during regeneration. Transcriptional profiling of isolated agat+ cells demonstrated enrichment for metabolic and transport-related genes, including those involved in creatine and ornithine metabolism, as well as secretory pathway components. Functional assays showed that creatine supplementation partially rescued regeneration defects following agat-2 knockdown, implicating creatine and related metabolites as critical factors for regenerative success. These findings redefine agat+ cells as a heterogeneous, metabolically active, and potentially secretory population that supports regeneration beyond their canonical role as transitional progenitors. Our results highlight the importance of differentiated support cells and their metabolic outputs in tissue regeneration, providing new insight into the coordination between progenitor populations and stem cells during whole-body regeneration in planarians.
{"title":"Metabolites produced by agat+ cells support regeneration in the planarian Schmidtea mediterranea","authors":"Aubrey M. Kent , Carlos Guerrero-Hernández , Carolyn Brewster , Sean McKinney , Jason A. Morrison , Mary C. McKinney , Eric J. Ross , Frederick G. Mann Jr. , Blair W. Benham-Pyle , Alejandro Sánchez Alvarado","doi":"10.1016/j.ydbio.2025.10.001","DOIUrl":"10.1016/j.ydbio.2025.10.001","url":null,"abstract":"<div><div>Planarians exhibit extraordinary regenerative abilities driven by pluripotent neoblasts, yet the roles of post-mitotic progenitor and differentiated cells in this process remain incompletely understood. Here, we investigate the function of <em>agat</em> <sup><em>+</em></sup> cells, epidermal progenitors expressing members of the arginine:glycine amidinotransferase (<em>agat</em>) gene family, in the regeneration of <em>Schmidtea mediterranea</em>. Comprehensive analysis of all five planarian <em>agat</em> paralogs revealed that <em>agat-1</em>, <em>-2</em>, <em>-3</em>, and <em>-4</em> are co-expressed in subepidermal populations enriched at wound sites, while <em>agat-5</em> is minimally expressed. RNAi-mediated knockdown of <em>agat-1</em> and <em>agat-2</em> resulted in severe defects: <em>agat-1</em> primarily disrupted tissue homeostasis, whereas <em>agat-2</em> specifically impaired blastema formation and stem cell maintenance during regeneration. Transcriptional profiling of isolated <em>agat</em> <sup>+</sup> cells demonstrated enrichment for metabolic and transport-related genes, including those involved in creatine and ornithine metabolism, as well as secretory pathway components. Functional assays showed that creatine supplementation partially rescued regeneration defects following <em>agat-</em>2 knockdown, implicating creatine and related metabolites as critical factors for regenerative success. These findings redefine <em>agat</em> <sup>+</sup> cells as a heterogeneous, metabolically active, and potentially secretory population that supports regeneration beyond their canonical role as transitional progenitors. Our results highlight the importance of differentiated support cells and their metabolic outputs in tissue regeneration, providing new insight into the coordination between progenitor populations and stem cells during whole-body regeneration in planarians.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 106-120"},"PeriodicalIF":2.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250260","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}
Ribosome biogenesis is critical for postembryonic development progression in Caenorhabditis elegans. Although maternally supplied ribosomes allow null mutants of ribosomal protein genes to complete embryogenesis, subsequent larval stages arrest if de novo ribosome production is compromised. Here, we compared null mutants in large (rpl-5, rpl-33) and small (rps-10, rps-23) ribosomal subunit genes with mutants defective in rRNA synthesis (rpoa-2 and rDNA loci). By tracking divisions of the mesoblast (M) cell, we discovered that large subunit mutations cause a stringent arrest in M cell proliferation, distinctly more severe than the partial arrests observed in small subunit and rRNA synthesis mutants. Unlike nutrient-deprived (starvation) L1 diapause, this arrest does not activate the cyclin-dependent kinase inhibitor CKI-1, suggesting a CKI-1-independent checkpoint. Gene expression analyses revealed that rpl-5(0) and rDNA(0) mutants share overexpression of genes involved in ribosomal RNA processing and ribosome assembly, whereas larvae depleted of the RNA polymerase I subunit RPOA-2 uniquely overexpress lipid metabolism genes. Tissue-specific manipulations previously confirmed that ribosomal insufficiency in a single tissue can impose a whole-organism developmental block. Genetic analyses further implicated the gap junction protein INX-14 and the TORC2 component SINH-1 as partial suppressors of the M cell arrest in small ribosomal subunit mutants (rps-23(0)), but not in large ribosomal subunit mutants (rpl-5(0)). Introducing null mutations in downstream TORC1/TORC2 kinases to a tissue-specific RPOA-2 depletion background similarly modulated growth arrest, suggesting that gap junction communication and TOR pathways converge upon a ribosomal stress checkpoint. Collectively, our findings highlight a unique, CKI-1-independent arrest driven by large ribosomal subunit gene loss and reveal how distinct signaling pathways coordinate postembryonic development in response to ribosome biogenesis defects.
{"title":"Ribosomal biogenesis defects trigger subunit specific developmental checkpoints via TOR signaling and gap junction in C. elegans","authors":"Agustian Surya , Qiuxia Zhao , Brittney Voigt , Rekha Rangan , Elif Sarinay Cenik","doi":"10.1016/j.ydbio.2025.10.003","DOIUrl":"10.1016/j.ydbio.2025.10.003","url":null,"abstract":"<div><div>Ribosome biogenesis is critical for postembryonic development progression in <em>Caenorhabditis elegans</em>. Although maternally supplied ribosomes allow null mutants of ribosomal protein genes to complete embryogenesis, subsequent larval stages arrest if de novo ribosome production is compromised. Here, we compared null mutants in large <em>(rpl-5, rpl-33</em>) and small (<em>rps-10, rps-23</em>) ribosomal subunit genes with mutants defective in rRNA synthesis (<em>rpoa-2</em> and <em>rDNA loci</em>). By tracking divisions of the mesoblast (M) cell, we discovered that large subunit mutations cause a stringent arrest in M cell proliferation, distinctly more severe than the partial arrests observed in small subunit and rRNA synthesis mutants. Unlike nutrient-deprived (starvation) L1 diapause, this arrest does not activate the cyclin-dependent kinase inhibitor CKI-1, suggesting a CKI-1-independent checkpoint. Gene expression analyses revealed that <em>rpl-5(0)</em> and <em>rDNA(0)</em> mutants share overexpression of genes involved in ribosomal RNA processing and ribosome assembly, whereas larvae depleted of the RNA polymerase I subunit RPOA-2 uniquely overexpress lipid metabolism genes. Tissue-specific manipulations previously confirmed that ribosomal insufficiency in a single tissue can impose a whole-organism developmental block. Genetic analyses further implicated the gap junction protein INX-14 and the TORC2 component SINH-1 as partial suppressors of the M cell arrest in small ribosomal subunit mutants (<em>rps-23(0)</em>), but not in large ribosomal subunit mutants (<em>rpl-5(0)</em>). Introducing null mutations in downstream TORC1/TORC2 kinases to a tissue-specific RPOA-2 depletion background similarly modulated growth arrest, suggesting that gap junction communication and TOR pathways converge upon a ribosomal stress checkpoint. Collectively, our findings highlight a unique, CKI-1-independent arrest driven by large ribosomal subunit gene loss and reveal how distinct signaling pathways coordinate postembryonic development in response to ribosome biogenesis defects.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 46-55"},"PeriodicalIF":2.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231639","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 : 2025-10-03DOI: 10.1016/j.ydbio.2025.10.002
Arzu Karahan
Model organisms are essential in science as they provide systems for studying conserved biological processes. In addition to widely used multicellular and unicellular models, tunicates have emerged as valuable model organisms in various biological fields due to their distinctive characteristics. As chordates with both sexual and asexual reproductive strategies and the capacity for whole-body regeneration (WBR), tunicates provide a unique system for regeneration studies. Although the majority of organisms display varying levels of regenerative ability, only a few can perform WBR; notably, botryllid ascidians (Stolidobranchia) are the sole documented group of chordates with WBR. Tunicates, a subphylum of over 3000 identified marine invertebrate species, are the closest living relatives of vertebrates. Botryllids comprise approximately 160 colonial tunicate species within the genera Botryllus and Botrylloides, less than ten of which have been shown to undergo WBR from vascular tissue. However, it remains unknown whether all botryllids are capable of WBR or not. Botryllus humilis was first observed in New Caledonia and has recently been identified in the Mediterranean Sea. In the present study, the blastogenic cycle and WBR capacity of B. humilis were monitored for the first time following the ablation of all zooids and buds. Two temperature conditions and two staging systems were used to record the blastogenetic cycle. Colonies completed their blastogenic cycle in 7 days at 21 °C and 38 ppt salinity, while this duration shortened to 4 days at 26 °C under the same salinity. Colony age appeared to influence the number of budded zooids during the blastogenic cycle. I also assessed the WBR capacity in B. humilis for the first time by inducing WBR at different stages of the blastogenic cycle. Regeneration was completed within 120–138 h post-surgery, and the first post-regeneration blastogenic cycle was completed within 2 days. This study provides valuable insights into B. humilis as a highly valuable model species for aging, stem cell dynamics, and WBR studies.
{"title":"Botryllus humilis: A promising new ascidian model for aging, stem cell dynamics, and whole-body regeneration","authors":"Arzu Karahan","doi":"10.1016/j.ydbio.2025.10.002","DOIUrl":"10.1016/j.ydbio.2025.10.002","url":null,"abstract":"<div><div>Model organisms are essential in science as they provide systems for studying conserved biological processes. In addition to widely used multicellular and unicellular models, tunicates have emerged as valuable model organisms in various biological fields due to their distinctive characteristics. As chordates with both sexual and asexual reproductive strategies and the capacity for whole-body regeneration (WBR), tunicates provide a unique system for regeneration studies. Although the majority of organisms display varying levels of regenerative ability, only a few can perform WBR; notably, botryllid ascidians (Stolidobranchia) are the sole documented group of chordates with WBR. Tunicates, a subphylum of over 3000 identified marine invertebrate species, are the closest living relatives of vertebrates. Botryllids comprise approximately 160 colonial tunicate species within the genera <em>Botryllus</em> and <em>Botrylloides</em>, less than ten of which have been shown to undergo WBR from vascular tissue. However, it remains unknown whether all botryllids are capable of WBR or not. <em>Botryllus humilis</em> was first observed in New Caledonia and has recently been identified in the Mediterranean Sea. In the present study, the blastogenic cycle and WBR capacity of <em>B. humilis</em> were monitored for the first time following the ablation of all zooids and buds. Two temperature conditions and two staging systems were used to record the blastogenetic cycle. Colonies completed their blastogenic cycle in 7 days at 21 °C and 38 ppt salinity, while this duration shortened to 4 days at 26 °C under the same salinity. Colony age appeared to influence the number of budded zooids during the blastogenic cycle. I also assessed the WBR capacity in <em>B. humilis</em> for the first time by inducing WBR at different stages of the blastogenic cycle. Regeneration was completed within 120–138 h post-surgery, and the first post-regeneration blastogenic cycle was completed within 2 days. This study provides valuable insights into <em>B. humilis</em> as a highly valuable model species for aging, stem cell dynamics, and WBR studies.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 56-65"},"PeriodicalIF":2.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231655","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 : 2025-09-30DOI: 10.1016/j.ydbio.2025.09.022
Visakuo Tsurho , Carla Gilliland , Jessica Ensing , Elizabeth A. VanSickle , Nathan J. Lanning , Paul R. Mark , Stephanie Grainger
Developmental NAD+ deficiency is associated with diverse congenital malformations. Congenital NAD deficiency disorder (CNDD) is a multisystem developmental condition characterized by cardiac, renal, vertebral, and limb anomalies, among others. It is caused by biallelic pathogenic variants in genes involved in the nicotinamide adenine dinucleotide (NAD+) synthesis pathway. CNDD anomalies overlap with clinical features described in vertebral-anal-cardiac-tracheoesophageal fistula-renal-limb (VACTERL) association, suggesting a possible shared etiological link through NAD+ deficiency. However, the aberrant developmental mechanisms of NAD+-deficient congenital anomalies remain poorly understood. To dynamically explore NAD+-deficiency-induced congenital malformations, we developed a zebrafish model of NAD+ disruption. Zebrafish embryos treated with 2-amino-1,3,4-thiadiazole (ATDA), a known NAD+ metabolism disruptor, exhibited cardiac, tail, spinal cord, and craniofacial defects, which were partially rescued by nicotinamide (NAM) in a dose-dependent manner. Our work establishes zebrafish as a useful model for investigating how NAD+ deficiency contributes to multisystem congenital anomalies.
{"title":"A zebrafish model of nicotinamide adenine dinucleotide (NAD+) deficiency-derived congenital disorders","authors":"Visakuo Tsurho , Carla Gilliland , Jessica Ensing , Elizabeth A. VanSickle , Nathan J. Lanning , Paul R. Mark , Stephanie Grainger","doi":"10.1016/j.ydbio.2025.09.022","DOIUrl":"10.1016/j.ydbio.2025.09.022","url":null,"abstract":"<div><div>Developmental NAD<sup>+</sup> deficiency is associated with diverse congenital malformations. Congenital NAD deficiency disorder (CNDD) is a multisystem developmental condition characterized by cardiac, renal, vertebral, and limb anomalies, among others. It is caused by biallelic pathogenic variants in genes involved in the nicotinamide adenine dinucleotide (NAD<sup>+</sup>) synthesis pathway. CNDD anomalies overlap with clinical features described in vertebral-anal-cardiac-tracheoesophageal fistula-renal-limb (VACTERL) association, suggesting a possible shared etiological link through NAD<sup>+</sup> deficiency. However, the aberrant developmental mechanisms of NAD<sup>+</sup>-deficient congenital anomalies remain poorly understood. To dynamically explore NAD<sup>+</sup>-deficiency-induced congenital malformations, we developed a zebrafish model of NAD<sup>+</sup> disruption. Zebrafish embryos treated with 2-amino-1,3,4-thiadiazole (ATDA), a known NAD<sup>+</sup> metabolism disruptor, exhibited cardiac, tail, spinal cord, and craniofacial defects, which were partially rescued by nicotinamide (NAM) in a dose-dependent manner. Our work establishes zebrafish as a useful model for investigating how NAD<sup>+</sup> deficiency contributes to multisystem congenital anomalies.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 271-277"},"PeriodicalIF":2.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211808","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 : 2025-09-29DOI: 10.1016/j.ydbio.2025.09.021
Piotr Świątek, Łukasz Gajda, Anna Z. Urbisz
<div><div>Clitellate annelids (Clitellata) are hermaphrodites with gonads localized in specific segments in the anterior body part. Localization of gonads and the structure of the reproductive systems are considered conservative traits of clitellate evolution and are used as crucial features in their taxonomy and in phylogenetic considerations. The study aimed to present the ovary morphology, histology, and ultrastructure in two <em>Delaya</em> species. The genus <em>Delaya</em> groups poorly known cave-living clitellate annelids, and their ovary organization and oogenesis are entirely unknown. Moreover, their taxonomic status is under debate. According to recent molecular analyses, <em>Delaya</em> and two other genera form the family Pelodrilidae, closely related to earthworms. To enhance our understanding of these cave-living animals' reproductive biology and provide new characters that may aid in phylogenetic considerations, the light and electron microscopic techniques were used to study the organization of the ovaries and the course of oogenesis in two species: one from a cave in Greece (<em>Delaya</em> sp. GR) and the other from a cave in France (<em>Delaya</em> sp. FR). In both species studied, two pairs of ovaries are located in two consecutive segments – XII and XIII. Each ovary consists of 3–5 functional units. The ovarian units are polarized: their apical parts (attached to the septum) contain oogonia and early meiotic cells, while the broader distal ends contain growing oocytes and nurse cells. Initially, Germline cyst formation in cells (oogonia and early meiotic cells) develop synchronously, forming syncytial cysts in which each cell is connected via a single ring canal to the central cytoplasm (cytophore). Then, during meiotic prophase (in diplotene), synchrony is lost, and it is likely that one cell per cyst begins accumulating nutrients and differentiating into an oocyte. As oocytes detach from the cyst and continue oogenesis as individual cells, the remaining cells stay interconnected, do not grow, and are regarded as nurse cells. Yolk absorption is not completed in the ovary; vitellogenic oocytes are transferred to the ovisacs, where they continue to accumulate nutrients. Ovisacs are paired, long, sac-like structures, extending through several body segments (XII-XV). <em>Delaya</em> produces mesolecithic eggs with prominent yolk spheres, lipid droplets, and glycogen granules. Only some minor differences were observed between the two studied species. The most notable difference concerns the cytophore shape and volume in cysts connecting nurse cells. In <em>Delaya</em> sp. FR, the cytophore is reticular and inconspicuous, whereas in <em>Delaya</em> sp. GR, the cytophore is more prominent and may contain nurse cell nuclei.</div><div>The obtained results confirm that the formation of the germline cysts equipped with the cytophore is a conservative phase of oogenesis in clitellates. Morphological observations suggest that in <em>Del
{"title":"Ovary organization and oogenesis in two species of cave-living clitellate annelids from the genus Delaya (Clitellata, Pelodrilidae)","authors":"Piotr Świątek, Łukasz Gajda, Anna Z. Urbisz","doi":"10.1016/j.ydbio.2025.09.021","DOIUrl":"10.1016/j.ydbio.2025.09.021","url":null,"abstract":"<div><div>Clitellate annelids (Clitellata) are hermaphrodites with gonads localized in specific segments in the anterior body part. Localization of gonads and the structure of the reproductive systems are considered conservative traits of clitellate evolution and are used as crucial features in their taxonomy and in phylogenetic considerations. The study aimed to present the ovary morphology, histology, and ultrastructure in two <em>Delaya</em> species. The genus <em>Delaya</em> groups poorly known cave-living clitellate annelids, and their ovary organization and oogenesis are entirely unknown. Moreover, their taxonomic status is under debate. According to recent molecular analyses, <em>Delaya</em> and two other genera form the family Pelodrilidae, closely related to earthworms. To enhance our understanding of these cave-living animals' reproductive biology and provide new characters that may aid in phylogenetic considerations, the light and electron microscopic techniques were used to study the organization of the ovaries and the course of oogenesis in two species: one from a cave in Greece (<em>Delaya</em> sp. GR) and the other from a cave in France (<em>Delaya</em> sp. FR). In both species studied, two pairs of ovaries are located in two consecutive segments – XII and XIII. Each ovary consists of 3–5 functional units. The ovarian units are polarized: their apical parts (attached to the septum) contain oogonia and early meiotic cells, while the broader distal ends contain growing oocytes and nurse cells. Initially, Germline cyst formation in cells (oogonia and early meiotic cells) develop synchronously, forming syncytial cysts in which each cell is connected via a single ring canal to the central cytoplasm (cytophore). Then, during meiotic prophase (in diplotene), synchrony is lost, and it is likely that one cell per cyst begins accumulating nutrients and differentiating into an oocyte. As oocytes detach from the cyst and continue oogenesis as individual cells, the remaining cells stay interconnected, do not grow, and are regarded as nurse cells. Yolk absorption is not completed in the ovary; vitellogenic oocytes are transferred to the ovisacs, where they continue to accumulate nutrients. Ovisacs are paired, long, sac-like structures, extending through several body segments (XII-XV). <em>Delaya</em> produces mesolecithic eggs with prominent yolk spheres, lipid droplets, and glycogen granules. Only some minor differences were observed between the two studied species. The most notable difference concerns the cytophore shape and volume in cysts connecting nurse cells. In <em>Delaya</em> sp. FR, the cytophore is reticular and inconspicuous, whereas in <em>Delaya</em> sp. GR, the cytophore is more prominent and may contain nurse cell nuclei.</div><div>The obtained results confirm that the formation of the germline cysts equipped with the cytophore is a conservative phase of oogenesis in clitellates. Morphological observations suggest that in <em>Del","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 13-34"},"PeriodicalIF":2.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205886","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 : 2025-09-26DOI: 10.1016/j.ydbio.2025.09.020
Jamie R. Shuda , Valerie G. Butler , Robert Vary , Darby W. Sweeney , Fernando L. Wagner , Steven A. Farber
BioEYES is a K-12 life science outreach program that uses zebrafish to teach Mendelian genetics through hands-on activities. The program has operated for 20+ years, promoting academic equity and fostering scientific literacy for all students. While middle school participants show knowledge gains and improved attitudes about science, ∼50% struggle to master foundational genetic concepts. To address this, the authors compared virtual vs. in-person programming, finding minimal differences in learning outcomes but higher gains on simpler survey questions. Rigorous assessments, however, reveal that many students retain only a basic understanding of genetics. Teaching single-gene inheritance, moreover, may reinforce racial stereotypes through "biological essentialism." To counter this, BioEYES staff will be piloting approaches that focus on human polygenic traits, such as skin color, that is taught alongside a hands-on experiment with a zebrafish pigment mutant. Future efforts emphasize developing curriculum around polygenic traits, gene-environment interactions, and challenging stereotypes about race, which research suggests could improve genetics comprehension while reducing racial stereotyping. We invite community feedback in these efforts to enhance K-12 genetics education strategies.
{"title":"The challenge of teaching K-12 genetic principles: A new approach emphasizing polygenic traits, gene-environment interactions, and genetic non-essentialism to improve genetics literacy and reduce racial stereotyping","authors":"Jamie R. Shuda , Valerie G. Butler , Robert Vary , Darby W. Sweeney , Fernando L. Wagner , Steven A. Farber","doi":"10.1016/j.ydbio.2025.09.020","DOIUrl":"10.1016/j.ydbio.2025.09.020","url":null,"abstract":"<div><div>BioEYES is a K-12 life science outreach program that uses zebrafish to teach Mendelian genetics through hands-on activities. The program has operated for 20+ years, promoting academic equity and fostering scientific literacy for all students. While middle school participants show knowledge gains and improved attitudes about science, ∼50% struggle to master foundational genetic concepts. To address this, the authors compared virtual vs. in-person programming, finding minimal differences in learning outcomes but higher gains on simpler survey questions. Rigorous assessments, however, reveal that many students retain only a basic understanding of genetics. Teaching single-gene inheritance, moreover, may reinforce racial stereotypes through \"biological essentialism.\" To counter this, BioEYES staff will be piloting approaches that focus on human polygenic traits, such as skin color, that is taught alongside a hands-on experiment with a zebrafish pigment mutant. Future efforts emphasize developing curriculum around polygenic traits, gene-environment interactions, and challenging stereotypes about race, which research suggests could improve genetics comprehension while reducing racial stereotyping. We invite community feedback in these efforts to enhance K-12 genetics education strategies.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 35-45"},"PeriodicalIF":2.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184787","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 : 2025-09-26DOI: 10.1016/j.ydbio.2025.09.019
Amber D. Ide, Kelsey A. Carpenter, Mohamed T. Elaswad, Katherine Opria, Kendersley Marcellin, Carla Gilliland, Stephanie Grainger
Hematopoietic stem and progenitor cells (HSPCs) are only generated during embryonic development, and their identity specification, emergence from the floor of the dorsal aorta, and proliferation are all tightly regulated by molecular mechanisms such as signaling cues. Among these, Wnt signaling is crucial for HSPC specification, differentiation, and self-renewal, requiring precise regulation for proper development and homeostasis. Wnt signaling begins when a Wnt ligand binds to cell surface receptors, such as those encoded by the frizzled gene family, activating intracellular pathways that regulate gene expression. Secreted frizzled-related proteins (Sfrps) are known to modulate Wnt signaling, acting as both agonists and antagonists. However, the in vivo roles of Sfrps in HSPC development are not fully understood. Here, we show that Sfrp1a influences zebrafish HSPC development and hematopoietic differentiation in a dose-dependent manner. Sfrp1a loss-of-function animals display an upregulation of canonical Wnt signaling, increased HSPC proliferation, and reduced differentiation into lymphoid and myeloid lineages. Conversely, low-dose overexpression of sfrp1a leads to decreased HSPC numbers and enhanced lymphoid differentiation. High-dose sfrp1a overexpression mimics the loss-of-function phenotype, with elevated canonical Wnt signaling, increased HSPCs, and decreased lymphoid and myeloid differentiation. These results emphasize the importance of dose-dependent Sfrp regulation, paralleling observations in hematopoietic cancers where SFRP1 variants can either promote or inhibit tumor development.
{"title":"Secreted frizzled-related protein 1a regulates hematopoietic development in a dose-dependent manner","authors":"Amber D. Ide, Kelsey A. Carpenter, Mohamed T. Elaswad, Katherine Opria, Kendersley Marcellin, Carla Gilliland, Stephanie Grainger","doi":"10.1016/j.ydbio.2025.09.019","DOIUrl":"10.1016/j.ydbio.2025.09.019","url":null,"abstract":"<div><div>Hematopoietic stem and progenitor cells (HSPCs) are only generated during embryonic development, and their identity specification, emergence from the floor of the dorsal aorta, and proliferation are all tightly regulated by molecular mechanisms such as signaling cues. Among these, Wnt signaling is crucial for HSPC specification, differentiation, and self-renewal, requiring precise regulation for proper development and homeostasis. Wnt signaling begins when a Wnt ligand binds to cell surface receptors, such as those encoded by the <em>frizzled</em> gene family, activating intracellular pathways that regulate gene expression. Secreted frizzled-related proteins (Sfrps) are known to modulate Wnt signaling, acting as both agonists and antagonists. However, the <em>in vivo</em> roles of Sfrps in HSPC development are not fully understood. Here, we show that Sfrp1a influences zebrafish HSPC development and hematopoietic differentiation in a dose-dependent manner. Sfrp1a loss-of-function animals display an upregulation of canonical Wnt signaling, increased HSPC proliferation, and reduced differentiation into lymphoid and myeloid lineages. Conversely, low-dose overexpression of <em>sfrp1a</em> leads to decreased HSPC numbers and enhanced lymphoid differentiation. High-dose <em>sfrp1a</em> overexpression mimics the loss-of-function phenotype, with elevated canonical Wnt signaling, increased HSPCs, and decreased lymphoid and myeloid differentiation. These results emphasize the importance of dose-dependent Sfrp regulation, paralleling observations in hematopoietic cancers where SFRP1 variants can either promote or inhibit tumor development.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 1-12"},"PeriodicalIF":2.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184991","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}
Vascular development is a pivotal aspect of embryogenesis, and its disruption can lead to developmental abnormalities or lethality. Although numerous studies have demonstrated a significant association between heme oxygenase 1 (Hmox1) and vascular biology, this link has not been reported so far during mouse embryonic development. Hmox1 is the rate-limiting enzyme that catalyzes the breakdown of heme to equimolar amounts of biliverdin, carbon monoxide, and ferrous iron. Here, we report that embryos lacking Hmox1 exhibit significant reductions in superficial blood vessel formation during mid-gestation, accompanied by organ-specific disruptions in vascular patterning. A comparative analysis of VEGF, VEGFR2, and CD31 revealed tissue-specific disruptions in angiogenic signaling and endothelial integrity in the brain, heart, and lungs of Hmox1-deficient embryos. The localization and abundance of these molecules were altered in affected organs, with isoform- and receptor subtype–specific expression changes raising the possibility of an impact on the structural integrity of developing vascular networks. These findings suggest that the absence of Hmox1 disrupts essential regulatory mechanisms required for angiogenesis, potentially contributing to the partial prenatal lethality observed in knockout embryos. Our results point to a previously unrecognized role for Hmox1 in regulating organ-specific vascular development during late gestation, with its deficiency leading to tissue-specific disruptions in angiogenesis and impaired blood vessel formation.
{"title":"VEGF and its receptors expression in relation to reduced vasculature phenotype in heme oxygenase 1 knockout mouse embryos","authors":"Meenakshi Rana , Gouri Nandi , Sidhant Jain , Divya Bajaj","doi":"10.1016/j.ydbio.2025.09.018","DOIUrl":"10.1016/j.ydbio.2025.09.018","url":null,"abstract":"<div><div>Vascular development is a pivotal aspect of embryogenesis, and its disruption can lead to developmental abnormalities or lethality. Although numerous studies have demonstrated a significant association between heme oxygenase 1 (Hmox1) and vascular biology, this link has not been reported so far during mouse embryonic development. Hmox1 is the rate-limiting enzyme that catalyzes the breakdown of heme to equimolar amounts of biliverdin, carbon monoxide, and ferrous iron. Here, we report that embryos lacking Hmox1 exhibit significant reductions in superficial blood vessel formation during mid-gestation, accompanied by organ-specific disruptions in vascular patterning. A comparative analysis of VEGF, VEGFR2, and CD31 revealed tissue-specific disruptions in angiogenic signaling and endothelial integrity in the brain, heart, and lungs of Hmox1-deficient embryos. The localization and abundance of these molecules were altered in affected organs, with isoform- and receptor subtype–specific expression changes raising the possibility of an impact on the structural integrity of developing vascular networks. These findings suggest that the absence of Hmox1 disrupts essential regulatory mechanisms required for angiogenesis, potentially contributing to the partial prenatal lethality observed in knockout embryos. Our results point to a previously unrecognized role for Hmox1 in regulating organ-specific vascular development during late gestation, with its deficiency leading to tissue-specific disruptions in angiogenesis and impaired blood vessel formation.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 264-276"},"PeriodicalIF":2.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181844","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 : 2025-09-24DOI: 10.1016/j.ydbio.2025.09.017
Ankita Walvekar , Shivangi Pandey , Siddhesh S. Kamat , Raj K. Ladher , Neha Vyas
Sonic hedgehog (Shh) is a pivotal morphogen in spinal cord development, orchestrating both ventral neural patterning and progenitor proliferation. How these distinct outcomes are specified has remained elusive. Here, we uncover that Shh is secreted via two biochemically and functionally distinct exosomal pools. A dense vesicle fraction, Shh-P150, drives Smoothened–Gli1 signalling to establish ventral progenitor identities, while a lighter pool, Shh-P450, activates a Smoothened–Gαi–dependent pathway that enhances progenitor proliferation without inducing ventral fate. We identify Rab7, a late endosomal regulator, as essential for Shh-P150 biogenesis and for notochord-mediated ventral neural patterning. Loss of Rab7 biases secretion toward the proliferative Shh-P450 pool and disrupts morphogenetic signalling. These findings establish exosomal packaging as a molecular switch that toggles Shh between its mitogenic and morphogenetic roles. By linking exosome biogenesis to developmental outcomes, our work reveals a novel mechanism that safeguards the balance between pattern formation and progenitor expansion during neural tube development, with implications for both developmental disorders and disease contexts where Shh signalling is misregulated.
Sonic hedgehog基因（Shh）在脊髓发育过程中是一个关键的形态因子，协调腹侧神经模式和祖细胞增殖。这些不同的结果是如何确定的仍然是难以捉摸的。在这里，我们发现Shh是通过两个生化和功能上不同的外泌体池分泌的。致密的囊泡片段sh - p150驱动Smoothened-Gli1信号以建立腹侧祖细胞身份，而较轻的囊泡片段sh - p450激活smoothened - g - αi依赖通路，增强祖细胞增殖而不诱导腹侧死亡。我们发现Rab7是一种晚期内体调节因子，对sh - p150的生物发生和脊索介导的腹侧神经模式至关重要。Rab7的缺失使分泌偏向增殖的sh - p450库，并破坏形态发生信号传导。这些发现确立了外泌体包装作为一个分子开关，在其有丝分裂和形态发生作用之间切换Shh。通过将外泌体生物发生与发育结果联系起来，我们的工作揭示了一种新的机制，该机制在神经管发育过程中保护模式形成和祖细胞扩张之间的平衡，这对发育障碍和Shh信号失调的疾病环境都有影响。
{"title":"The patterning and proliferation roles of Shh are partitioned on distinct exosomes","authors":"Ankita Walvekar , Shivangi Pandey , Siddhesh S. Kamat , Raj K. Ladher , Neha Vyas","doi":"10.1016/j.ydbio.2025.09.017","DOIUrl":"10.1016/j.ydbio.2025.09.017","url":null,"abstract":"<div><div>Sonic hedgehog (Shh) is a pivotal morphogen in spinal cord development, orchestrating both ventral neural patterning and progenitor proliferation. How these distinct outcomes are specified has remained elusive. Here, we uncover that Shh is secreted via two biochemically and functionally distinct exosomal pools. A dense vesicle fraction, Shh-P150, drives Smoothened–Gli1 signalling to establish ventral progenitor identities, while a lighter pool, Shh-P450, activates a Smoothened–Gαi–dependent pathway that enhances progenitor proliferation without inducing ventral fate. We identify Rab7, a late endosomal regulator, as essential for Shh-P150 biogenesis and for notochord-mediated ventral neural patterning. Loss of Rab7 biases secretion toward the proliferative Shh-P450 pool and disrupts morphogenetic signalling. These findings establish exosomal packaging as a molecular switch that toggles Shh between its mitogenic and morphogenetic roles. By linking exosome biogenesis to developmental outcomes, our work reveals a novel mechanism that safeguards the balance between pattern formation and progenitor expansion during neural tube development, with implications for both developmental disorders and disease contexts where Shh signalling is misregulated.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Pages 239-254"},"PeriodicalIF":2.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155730","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 : 2025-09-23DOI: 10.1016/j.ydbio.2025.09.015
Xiangyang Liu , Jianfeng Wang , Youshi Chen , Hongjun Shi
{"title":"Corrigendum to “A low-cost, high-throughput pipeline for 3D imaging of embryonic mouse hearts using lightsheet microscopy” [Develop. Biol. 527 (2025) 26–38]","authors":"Xiangyang Liu , Jianfeng Wang , Youshi Chen , Hongjun Shi","doi":"10.1016/j.ydbio.2025.09.015","DOIUrl":"10.1016/j.ydbio.2025.09.015","url":null,"abstract":"","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"528 ","pages":"Page 216"},"PeriodicalIF":2.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118840","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}
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