Pub Date : 2025-12-19DOI: 10.1016/j.ydbio.2025.12.012
Malgorzata Kloc PhD, Dr. Sc.
{"title":"Editorial: “Oogenesis: following the pattern and eccentricities”","authors":"Malgorzata Kloc PhD, Dr. Sc.","doi":"10.1016/j.ydbio.2025.12.012","DOIUrl":"10.1016/j.ydbio.2025.12.012","url":null,"abstract":"","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 258-259"},"PeriodicalIF":2.1,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800292","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 : 2025-12-18DOI: 10.1016/j.ydbio.2025.12.010
Runqiu Han , Ning Ding , Shuqi Li, Wei Liu, Yankai Liu, Qingnan Tian
Although some animals are capable of regenerating organs, the mechanisms by which this is achieved are poorly understood. For most tissues and organs, the spatiotemporal dynamics of stem cell differentiation and the fate of tissue that existed prior to injury have not been characterized systematically. Planarians are able to regenerate any missing part of their body after injury, and are thus ideally suited for investigating organ regeneration. Here, we show that Rap1/RhoA/Cofilin pathway is responsible for the intestinal and neural regeneration in planarians. We found that Rap1 is enriched in planarian eyes and intestinal tissues. Both Rap1(RNAi) and RhoA(RNAi) animal commence with decreased expression of gut-specific progenitor marker. Meanwhile, knockdown of Cofilin, which co-expressed with RhoA, caused similar phenotypes with RhoA(RNAi). Moreover, we identified Rnd as a negative regulator of RhoA, the silencing of which recover the defects observed in RhoA(RNAi) animals. Therefore, our findings indicate that Rap1/RhoA/Cofilin pathway is an important regulator of the intestinal regeneration.
{"title":"The RhoA signaling pathway is required for planarian intestinal regeneration","authors":"Runqiu Han , Ning Ding , Shuqi Li, Wei Liu, Yankai Liu, Qingnan Tian","doi":"10.1016/j.ydbio.2025.12.010","DOIUrl":"10.1016/j.ydbio.2025.12.010","url":null,"abstract":"<div><div>Although some animals are capable of regenerating organs, the mechanisms by which this is achieved are poorly understood. For most tissues and organs, the spatiotemporal dynamics of stem cell differentiation and the fate of tissue that existed prior to injury have not been characterized systematically. Planarians are able to regenerate any missing part of their body after injury, and are thus ideally suited for investigating organ regeneration. Here, we show that <em>Rap1</em>/<em>RhoA</em>/<em>Cofilin</em> pathway is responsible for the intestinal and neural regeneration in planarians. We found that <em>Rap1</em> is enriched in planarian eyes and intestinal tissues. Both <em>Rap1(RNAi)</em> and <em>RhoA</em>(<em>RNAi)</em> animal commence with decreased expression of gut-specific progenitor marker. Meanwhile, knockdown of <em>Cofilin</em>, which co-expressed with <em>RhoA</em>, caused similar phenotypes with <em>RhoA(RNAi)</em>. Moreover, we identified <em>Rnd</em> as a negative regulator of <em>RhoA</em>, the silencing of which recover the defects observed in <em>RhoA(RNAi)</em> animals. Therefore, our findings indicate that <em>Rap1</em>/<em>RhoA</em>/<em>Cofilin</em> pathway is an important regulator of the intestinal regeneration.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 248-257"},"PeriodicalIF":2.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800267","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 : 2025-12-15DOI: 10.1016/j.ydbio.2025.12.006
Ruixun Wang, Matthias Pechmann
The early embryogenesis of many spiders involves the formation of a radially symmetric germ disc. While the cells of the rim of this germ disc develops into anterior structures, the center of the disc will form the posteriorly located segment addition zone of the embryo. Therefore, germ disc formation sets the anterior-posterior (AP) body axis of spider embryos. The early spider egg is a spherical structure with no apparent asymmetry. So far it is unclear if the placement of the germ disc is a predetermined or a stochastic process.
For this study, we have re-analysed early spider embryogenesis and found a link between the position of the polar bodies and the formation of the germ disc. Using cell tracking and time-lapse recordings of live embryos injected with the live cell nuclear stain SPY555-DNA, we show that the germ disc forms opposite to the polar bodies. Our results suggest that germ disc formation in the common house spider Parasteatoda tepidariorum is not a stochastic but a pre-determined process. By analyzing germ disc formation in a basally branching cobweb spider and a curtain-web spider, we provide evidence that the initial process of germ disc placement might be conserved between araneomorph and mygalomorph spider species.
{"title":"Polar bodies serve as a landmark for anteroposterior axis formation in spiders","authors":"Ruixun Wang, Matthias Pechmann","doi":"10.1016/j.ydbio.2025.12.006","DOIUrl":"10.1016/j.ydbio.2025.12.006","url":null,"abstract":"<div><div>The early embryogenesis of many spiders involves the formation of a radially symmetric germ disc. While the cells of the rim of this germ disc develops into anterior structures, the center of the disc will form the posteriorly located segment addition zone of the embryo. Therefore, germ disc formation sets the anterior-posterior (AP) body axis of spider embryos. The early spider egg is a spherical structure with no apparent asymmetry. So far it is unclear if the placement of the germ disc is a predetermined or a stochastic process.</div><div>For this study, we have re-analysed early spider embryogenesis and found a link between the position of the polar bodies and the formation of the germ disc. Using cell tracking and time-lapse recordings of live embryos injected with the live cell nuclear stain SPY555-DNA, we show that the germ disc forms opposite to the polar bodies. Our results suggest that germ disc formation in the common house spider <em>Parasteatoda tepidariorum</em> is not a stochastic but a pre-determined process. By analyzing germ disc formation in a basally branching cobweb spider and a curtain-web spider, we provide evidence that the initial process of germ disc placement might be conserved between araneomorph and mygalomorph spider species.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 265-273"},"PeriodicalIF":2.1,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773766","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 : 2025-12-13DOI: 10.1016/j.ydbio.2025.12.009
Mahesh K. Nayak , Miaomiao Du , Rene Vielman Quevedo , Kristina Ly , Celia R. Bloom , Martín L. Basch , Justine Renauld
The inner ear is responsible for hearing and balance. During development, the inner ear undergoes extensive morphogenesis to create a coil shaped cochlea and three semicircular canals from an original flat otic placode. During this morphogenesis, neural crest cells migrate into the inner ear in formation to become either glial cells or melanocytes. The glial cells are located in the cochleo-vestibular ganglion and the melanocytes reside in the stria vascularis in the cochlea and dark cells zone in the vestibule. The stria vascularis pumps potassium ions into the scala media, generating a positive endocochlear potential which is crucial to the mechanosensory cells for auditory signal transduction. Any defect in strial cells leads to the dysregulation of ionic composition of the endolymph, ultimately resulting in deafness. Despite this, we still do not know exactly how the stria vascularis develops and functions.
To date, there is an absence of Cre driver mouse lines that effectively facilitate the study of individual cell development and functions within the stria vascularis, limiting our ability to understand strial deafness. Furthermore, the use of CreER transgenic mice lines introduces the possibility of poor recombination and non-specific expression. Therefore, it is necessary to establish a mouse line targeting each cell type within the stria vascularis.
The present study aims to determine the most appropriate CreER transgenic line targeting the melanocytes of the inner ear by comparing three CreER mouse lines related to melanocyte development: Pax3, Dct, and Tyr. The CreER mice were crossed with tdTomato reporter mice and induced with tamoxifen at three time points E11.5, P0, and P28 to study the spatiotemporal recombination in the inner ear. We quantify the recombination efficiency in the intermediate cells at each time point and identify important variations in both efficiency and specificity for the three lines. This study focusing on cochlear and vestibular melanocytes provides a much-needed tool to study melanocyte development and function in the inner ear with spatiotemporal control.
{"title":"Targeting the melanocytes of the inner ear: A comparison of different CreER lines","authors":"Mahesh K. Nayak , Miaomiao Du , Rene Vielman Quevedo , Kristina Ly , Celia R. Bloom , Martín L. Basch , Justine Renauld","doi":"10.1016/j.ydbio.2025.12.009","DOIUrl":"10.1016/j.ydbio.2025.12.009","url":null,"abstract":"<div><div>The inner ear is responsible for hearing and balance. During development, the inner ear undergoes extensive morphogenesis to create a coil shaped cochlea and three semicircular canals from an original flat otic placode. During this morphogenesis, neural crest cells migrate into the inner ear in formation to become either glial cells or melanocytes. The glial cells are located in the cochleo-vestibular ganglion and the melanocytes reside in the stria vascularis in the cochlea and dark cells zone in the vestibule. The stria vascularis pumps potassium ions into the <em>scala media</em>, generating a positive endocochlear potential which is crucial to the mechanosensory cells for auditory signal transduction. Any defect in strial cells leads to the dysregulation of ionic composition of the endolymph, ultimately resulting in deafness. Despite this, we still do not know exactly how the stria vascularis develops and functions.</div><div>To date, there is an absence of Cre driver mouse lines that effectively facilitate the study of individual cell development and functions within the stria vascularis, limiting our ability to understand strial deafness. Furthermore, the use of CreER transgenic mice lines introduces the possibility of poor recombination and non-specific expression. Therefore, it is necessary to establish a mouse line targeting each cell type within the stria vascularis.</div><div>The present study aims to determine the most appropriate CreER transgenic line targeting the melanocytes of the inner ear by comparing three CreER mouse lines related to melanocyte development: <em>Pax3</em>, <em>Dct</em>, and <em>Tyr</em>. The CreER mice were crossed with tdTomato reporter mice and induced with tamoxifen at three time points E11.5, P0, and P28 to study the spatiotemporal recombination in the inner ear. We quantify the recombination efficiency in the intermediate cells at each time point and identify important variations in both efficiency and specificity for the three lines. This study focusing on cochlear and vestibular melanocytes provides a much-needed tool to study melanocyte development and function in the inner ear with spatiotemporal control.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 224-233"},"PeriodicalIF":2.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762612","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 : 2025-12-11DOI: 10.1016/j.ydbio.2025.12.008
Yuki S. Kogure , Satoru Okuda , Kotaro Oka , Kohji Hotta
Axial rotation (AR), a morphogenetic movement that reshapes the body axis, is widely observed in chordates, including mice and rats. AR involves complex three-dimensional deformations; however, its geometric characteristics and regulatory mechanisms remain poorly understood. Here, using the chordate Ciona robusta (Ciona intestinalis type A), we demonstrate that AR consists of two differentially regulated components—leftward bending and clockwise twisting along the anterior–posterior axis. A comparison between chorionated and dechorionated embryos revealed that dechorionation randomized the bending direction, while twisting remained consistently clockwise. Inhibition of TGF-β signaling with SB431542 randomized both deformations. Quantitative analysis of twisting angles indicated uniform clockwise twisting along the axis, peaking during the tailbud stage and proceeding in the tail region, independent of the tip, trunk, or myofibril patterning. Although overall twisting was reduced under TGF-β inhibition, the tail exhibited disorganized twisting. The sum of absolute twisting-angle differences in every 10 μm remained comparable to the wild type (WT). This suggests that twisting is intrinsically generated, while TGF-β signaling aligns local twisting into a coordinated global direction. Our findings dissected the mechanisms of AR in Ciona and highlight the multilayered regulation underlying the morphogenesis of the chordate body plan and providing a foundation for understanding its biomechanical and molecular bases.
轴向旋转（AR）是一种重塑身体轴的形态发生运动，在脊索动物中广泛观察到，包括小鼠和大鼠。AR涉及复杂的三维变形；然而，其几何特征和调控机制仍然知之甚少。在这里，我们使用脊索动物robusta (chiona nestiinalis type A)，证明AR由两个不同调节的成分组成——沿前后轴向左弯曲和顺时针扭曲。绒毛膜剥离胚胎与去绒毛膜剥离胚胎的比较表明，去绒毛膜剥离胚胎的弯曲方向随机化，而扭曲方向始终保持顺时针方向。SB431542对TGF-β信号的抑制随机化了这两种变形。扭曲角度的定量分析表明，沿轴线均匀顺时针扭曲，在尾芽阶段达到峰值，并在尾部区域进行，与尖端、躯干或肌原纤维的模式无关。虽然在TGF-β抑制作用下，整体扭曲减少，但尾部扭曲呈现无组织。每10 μm的绝对扭转角差之和与野生型（WT）相当。这表明扭曲是内在产生的，而TGF-β信号将局部扭曲对齐到协调的全局方向。我们的研究结果剖析了AR在Ciona中的机制，并强调了脊索动物体表形态发生的多层调控，为理解其生物力学和分子基础提供了基础。
{"title":"Axial rotation comprises concurrent twisting and bending as distinct morphogenetic components in Ciona","authors":"Yuki S. Kogure , Satoru Okuda , Kotaro Oka , Kohji Hotta","doi":"10.1016/j.ydbio.2025.12.008","DOIUrl":"10.1016/j.ydbio.2025.12.008","url":null,"abstract":"<div><div>Axial rotation (AR), a morphogenetic movement that reshapes the body axis, is widely observed in chordates, including mice and rats. AR involves complex three-dimensional deformations; however, its geometric characteristics and regulatory mechanisms remain poorly understood. Here, using the chordate <em>Ciona robusta</em> (<em>Ciona intestinalis</em> type A), we demonstrate that AR consists of two differentially regulated components—leftward bending and clockwise twisting along the anterior–posterior axis. A comparison between chorionated and dechorionated embryos revealed that dechorionation randomized the bending direction, while twisting remained consistently clockwise. Inhibition of TGF-β signaling with SB431542 randomized both deformations. Quantitative analysis of twisting angles indicated uniform clockwise twisting along the axis, peaking during the tailbud stage and proceeding in the tail region, independent of the tip, trunk, or myofibril patterning. Although overall twisting was reduced under TGF-β inhibition, the tail exhibited disorganized twisting. The sum of absolute twisting-angle differences in every 10 μm remained comparable to the wild type (WT). This suggests that twisting is intrinsically generated, while TGF-β signaling aligns local twisting into a coordinated global direction. Our findings dissected the mechanisms of AR in <em>Ciona</em> and highlight the multilayered regulation underlying the morphogenesis of the chordate body plan and providing a foundation for understanding its biomechanical and molecular bases.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 234-247"},"PeriodicalIF":2.1,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741513","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 : 2025-12-09DOI: 10.1016/j.ydbio.2025.12.007
Paul P.R. Iyyanar , Rolf W. Stottmann
Human congenital anomalies account for twice the mortality of childhood cancer. Despite advancements in genome sequencing and transgenic mouse models that have aided in understanding their pathogenesis, significant gaps remain. Through a forward genetics approach, we previously discovered the hypo-morphic anteater allele of Cse1l which displayed variable craniofacial phenotypes. To circumvent the variability seen in this model, we generated a conditional allele of Cse1l and genetically ablated it in the dorsal midline giving rise to portions of the nervous system and the cranial neural crest cells using the Wnt1-Cre2 driver. Our analysis revealed that Wnt1-Cre2; Cse1lCRISPR/flox embryos exhibited severe malformations in the forebrain, midbrain, and hindbrain, accompanied by a dramatic hypoplasia of the frontonasal, maxillary, and mandibular processes, and the second pharyngeal arch. Wnt1-Cre2; Cse1lCRISPR/flox embryos were embryonic lethal by E11.5 likely due to proliferative defects in the ventricular myocardium. Wnt1-Cre2; Cse1lCRISPR/flox embryos exhibited consistently increased apoptosis at E9.5 in the affected tissues along with an increase in p53 expression. These data together show a previously unknown critical function of CSE1L in neural crest cell survival during development.
{"title":"Cse1l is critical for cell survival, craniofacial and cardiac development","authors":"Paul P.R. Iyyanar , Rolf W. Stottmann","doi":"10.1016/j.ydbio.2025.12.007","DOIUrl":"10.1016/j.ydbio.2025.12.007","url":null,"abstract":"<div><div>Human congenital anomalies account for twice the mortality of childhood cancer. Despite advancements in genome sequencing and transgenic mouse models that have aided in understanding their pathogenesis, significant gaps remain. Through a forward genetics approach, we previously discovered the hypo-morphic <em>anteater</em> allele of <em>Cse1l</em> which displayed variable craniofacial phenotypes. To circumvent the variability seen in this model, we generated a conditional allele of <em>Cse1l</em> and genetically ablated it in the dorsal midline giving rise to portions of the nervous system and the cranial neural crest cells using the <em>Wnt1-Cre</em>2 driver. Our analysis revealed that <em>Wnt1-Cre2; Cse1l</em><sup><em>CRISPR/flox</em></sup> embryos exhibited severe malformations in the forebrain, midbrain, and hindbrain, accompanied by a dramatic hypoplasia of the frontonasal, maxillary, and mandibular processes, and the second pharyngeal arch. <em>Wnt1-Cre2; Cse1l</em><sup><em>CRISPR/flox</em></sup> embryos were embryonic lethal by E11.5 likely due to proliferative defects in the ventricular myocardium. <em>Wnt1-Cre2; Cse1l</em><sup><em>CRISPR/flox</em></sup> embryos exhibited consistently increased apoptosis at E9.5 in the affected tissues along with an increase in p53 expression. These data together show a previously unknown critical function of CSE1L in neural crest cell survival during development.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 188-198"},"PeriodicalIF":2.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733053","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 : 2025-12-08DOI: 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}
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