Pub Date : 2025-11-17DOI: 10.1016/j.ydbio.2025.11.010
Sydney E. Christensen , Maria Ali , Jorden N. Holland, Bruce B. Riley
The zebrafish otic vesicle initially develops with only two sensory maculae, each with distinct functions. The anterior utricular macula is indispensable for vestibular function, while the posterior saccular macula is the primary auditory endorgan in zebrafish. The unique identities of these maculae are specified in the early otic vesicle by differing levels of Fgf vs. Shh signaling, but few downstream effectors have been identified. pou3f3b is the only saccule-specific marker known, but its function has not been established. We generated a knockout allele of pou3f3b and found that it causes a persistent delay in accumulation of saccular hair cells due to a failure to activate saccular expression of fgf3. In addition, saccular hair cells exhibit reduced expression of Otoferlin caused by ectopic expression of neurog1. Defects in saccular hair cell development are fully rescued by misexpressing fgf3 or knocking down neurog1. Misexpression of pou3f3b causes loss of utricular pax5 expression and further truncates neurog1 in the posterior otic vesicle but does not otherwise alter macular development. In addition to regulating saccular development, pou3f3b is also expressed in a previously undescribed population of non-neuronal cells that delaminate from the otic vesicle and migrate together with developing neuroblasts to promote their maturation. Mutant neuroblasts show a marked delay in activation of expression of neurod1, causing a transient delay in accumulation of mature SAG neurons. Thus pou3f3b is required for timely development of SAG neurons and saccular/auditory hair cells.
{"title":"Zebrafish pou3f3b controls saccular/auditory development and marks non-neuronal cells that delaminate from the otic vesicle to promote neuroblast maturation","authors":"Sydney E. Christensen , Maria Ali , Jorden N. Holland, Bruce B. Riley","doi":"10.1016/j.ydbio.2025.11.010","DOIUrl":"10.1016/j.ydbio.2025.11.010","url":null,"abstract":"<div><div>The zebrafish otic vesicle initially develops with only two sensory maculae, each with distinct functions. The anterior utricular macula is indispensable for vestibular function, while the posterior saccular macula is the primary auditory endorgan in zebrafish. The unique identities of these maculae are specified in the early otic vesicle by differing levels of Fgf vs. Shh signaling, but few downstream effectors have been identified. <em>pou3f3b</em> is the only saccule-specific marker known, but its function has not been established. We generated a knockout allele of <em>pou3f3b</em> and found that it causes a persistent delay in accumulation of saccular hair cells due to a failure to activate saccular expression of <em>fgf3.</em> In addition, saccular hair cells exhibit reduced expression of Otoferlin caused by ectopic expression of <em>neurog1</em>. Defects in saccular hair cell development are fully rescued by misexpressing <em>fgf3</em> or knocking down <em>neurog1</em>. Misexpression of <em>pou3f3b</em> causes loss of utricular <em>pax5</em> expression and further truncates <em>neurog1</em> in the posterior otic vesicle but does not otherwise alter macular development. In addition to regulating saccular development, <em>pou3f3b</em> is also expressed in a previously undescribed population of non-neuronal cells that delaminate from the otic vesicle and migrate together with developing neuroblasts to promote their maturation. Mutant neuroblasts show a marked delay in activation of expression of <em>neurod1</em>, causing a transient delay in accumulation of mature SAG neurons. Thus <em>pou3f3b</em> is required for timely development of SAG neurons and saccular/auditory hair cells.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 38-48"},"PeriodicalIF":2.1,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556491","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 : 2025-11-16DOI: 10.1016/j.ydbio.2025.11.008
Sowmya Priya Manoharan , Suvathika Gnanaselvan , Suriya Prakash Ramakrishnan , Sangilimuthu Alagar Yadav , L. Srimathi Priya , Manikandan Ayyar , Lalitha Gnanasekaran , M. Santhamoorthy , S. Santhoshkumar
The understanding of how drugs interact with carrier proteins is crucial in the field of pharmacology and the life sciences, especially in the field of drug invention. In the present work described the molecular interaction of pharmaceutically important phyto-molecule khellin on bovine serum albumin. Khellin is recognized for its ability to widen blood vessels, making it useful for heart health. It's a major component of the plant Ammi visnaga and Dioscorea species helps to protect the heart. Bovine serum albumin (BSA) is a model protein of Human serum albumin hence, BSA has been used for drug-binding properties studies. Various biophysical techniques to examine the interactions between khellin and BSA. The biophysical techniques such as fluorescence quenching by fluorescence spectroscopy studies, micro-environmental changes by synchronous fluorescence, protein structural changes by circular dichroism spectroscopy, molecular docking, ADMET properties studies, SWISS Target Prediction for target analysis and pharmacokinetic analysis by insilico. The Khellin-BSA interaction was examined using fluorescence analysis, which showed that the binding constant was 1.29 ± 0.2 × 1012 M−1 and binding free energy was −7.99 kcal/mol by invitro. The binding energy was compared with computation molecular docking studies of ligand and protein interaction showed the binding energy of −5.1 kcal/mol. It is nearer to the in vitro binding energy values of khellin on BSA. The micro-environmental changes of the ligand-protein complex were observed with peak shifts at Δλ15 for tyrosine, Δλ60 for tryptophane, and Δλ90 for phenylalanine. Also, the secondary structural changes of BSA after titrating the khellin were observed and found that there were secondary structural changes in the free BSA after adding the khellin. With possible targets found through SWISS Target Prediction, khellin is a promising druggable candidate, according to ADMET analysis, which revealed zero violations. Finally, we concluded that the Phyto-active constituent khellin possesses good binding affinity on BSA. Further, it can be taken for drug discovery experiments on clinical trials.
{"title":"Evaluation of molecular interaction studies of khellin on bovine serum albumin through various biophysical approaches","authors":"Sowmya Priya Manoharan , Suvathika Gnanaselvan , Suriya Prakash Ramakrishnan , Sangilimuthu Alagar Yadav , L. Srimathi Priya , Manikandan Ayyar , Lalitha Gnanasekaran , M. Santhamoorthy , S. Santhoshkumar","doi":"10.1016/j.ydbio.2025.11.008","DOIUrl":"10.1016/j.ydbio.2025.11.008","url":null,"abstract":"<div><div>The understanding of how drugs interact with carrier proteins is crucial in the field of pharmacology and the life sciences, especially in the field of drug invention. In the present work described the molecular interaction of pharmaceutically important phyto-molecule khellin on bovine serum albumin. Khellin is recognized for its ability to widen blood vessels, making it useful for heart health. It's a major component of the plant <em>Ammi visnaga</em> and <em>Dioscorea</em> species helps to protect the heart. Bovine serum albumin (BSA) is a model protein of Human serum albumin hence, BSA has been used for drug-binding properties studies. Various biophysical techniques to examine the interactions between khellin and BSA. The biophysical techniques such as fluorescence quenching by fluorescence spectroscopy studies, micro-environmental changes by synchronous fluorescence, protein structural changes by circular dichroism spectroscopy, molecular docking, ADMET properties studies, SWISS Target Prediction for target analysis and pharmacokinetic analysis by <em>insilico</em>. The Khellin-BSA interaction was examined using fluorescence analysis, which showed that the binding constant was 1.29 ± 0.2 × 10<sup>12</sup> M<sup>−1</sup> and binding free energy was −7.99 kcal/mol by <em>in</em> <em>vitro</em>. The binding energy was compared with computation molecular docking studies of ligand and protein interaction showed the binding energy of −5.1 kcal/mol. It is nearer to the in vitro binding energy values of khellin on BSA. The micro-environmental changes of the ligand-protein complex were observed with peak shifts at Δλ15 for tyrosine, Δλ60 for tryptophane, and Δλ90 for phenylalanine. Also, the secondary structural changes of BSA after titrating the khellin were observed and found that there were secondary structural changes in the free BSA after adding the khellin. With possible targets found through SWISS Target Prediction, khellin is a promising druggable candidate, according to ADMET analysis, which revealed zero violations. Finally, we concluded that the Phyto-active constituent khellin possesses good binding affinity on BSA. Further, it can be taken for drug discovery experiments on clinical trials.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 49-56"},"PeriodicalIF":2.1,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548590","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 : 2025-11-14DOI: 10.1016/j.ydbio.2025.11.003
Hannah E. Jones , Kelsey A. Abrams , Sol Kim , Katherine A. Fantauzzo , Julie A. Siegenthaler
Perivascular fibroblasts (PVFs) are a cell type associated with large diameter blood vessels in the brain and spinal cord parenchyma and leptomeninges. PVFs have previously defined roles in injury and neuroinflammatory diseases and predicted roles in supporting neurovascular function. The temporal dynamics of PVF development in the pre- and postnatal cerebral cortex have recently been described, however the molecular mechanisms that underly PVF development have not been identified. PVFs express both platelet-derived growth factor receptors (PDGFRs), PDGFRα and PDGFRβ. Here we investigate the role of PDGF signaling in PVF development. We use immunohistochemistry and RNA transcript detection methods to show developmental expression of PDGFRs by PVFs and examine distribution of PDGF ligand expression in the brain. We show that postnatal deletion of PDGFRα in fibroblasts using the Col1a2-CreERT mouse line impairs PVF coverage of cerebral vessels at postnatal day 10. Perivascular macrophages, a cell type previously shown to co-develop with PVFs, have impaired cerebral vessel coverage in conditional mutants that is similar to PVF coverage defects. This work establishes a requirement for PDGFRα signaling in PVF development and may shed light upon the potential pathways that are over-activated in PVFs in injury and disease contexts.
{"title":"PDGFRα is required for postnatal cerebral perivascular fibroblast development","authors":"Hannah E. Jones , Kelsey A. Abrams , Sol Kim , Katherine A. Fantauzzo , Julie A. Siegenthaler","doi":"10.1016/j.ydbio.2025.11.003","DOIUrl":"10.1016/j.ydbio.2025.11.003","url":null,"abstract":"<div><div>Perivascular fibroblasts (PVFs) are a cell type associated with large diameter blood vessels in the brain and spinal cord parenchyma and leptomeninges. PVFs have previously defined roles in injury and neuroinflammatory diseases and predicted roles in supporting neurovascular function. The temporal dynamics of PVF development in the pre- and postnatal cerebral cortex have recently been described, however the molecular mechanisms that underly PVF development have not been identified. PVFs express both platelet-derived growth factor receptors (PDGFRs), PDGFRα and PDGFRβ. Here we investigate the role of PDGF signaling in PVF development. We use immunohistochemistry and RNA transcript detection methods to show developmental expression of PDGFRs by PVFs and examine distribution of PDGF ligand expression in the brain. We show that postnatal deletion of PDGFRα in fibroblasts using the <em>Col1a2-CreERT</em> mouse line impairs PVF coverage of cerebral vessels at postnatal day 10. Perivascular macrophages, a cell type previously shown to co-develop with PVFs, have impaired cerebral vessel coverage in conditional mutants that is similar to PVF coverage defects. This work establishes a requirement for PDGFRα signaling in PVF development and may shed light upon the potential pathways that are over-activated in PVFs in injury and disease contexts.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534058","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 : 2025-11-14DOI: 10.1016/j.ydbio.2025.11.004
Katerina Cihakova , Ravindra Naraine , Viktoriia Hantzsch , Roman Franek , Martin Psenicka , Radek Sindelka
In many species, the differential localization of RNAs along the animal-vegetal axis is established during oogenesis. The resulting asymmetry is essential for axis formation, germ layer patterning, and cell fate determination, especially in fish and amphibians. In recent years, research in this field has focused mainly on zebrafish, which raises the question about the conservation of localization processes across all teleost species. Although extant teleost species utilize meroblastic cleavage only, there are extreme differences in their oocyte size. These differences are fundamentally linked to each species' life history. Some have rapid embryonic development, while embryos of other species, like salmonids, take weeks to develop. This might have consequences on the spatial distribution of biomolecules during oogenesis and their relocalization during early embryogenesis. Yet, our knowledge is based on data from small-sized oocyte species with rapid development only (e.g. zebrafish). In this study, we performed a spatially resolved TOMO-seq method on early embryos of the rainbow trout, a species characterized by prolonged embryonic development and large oocytes, and compared it with zebrafish. We revealed that the maternal pre-patterned localization of transcripts can be disrupted in the early embryo by two main mechanisms: de novo transcription and degradation. The most prominent change can be seen in the emerging blastodisc in the animal pole, where there is a significant increase in localized transcripts. In contrast with research suggesting active relocalization of RNAs by ooplasmic streaming in zebrafish, we hypothesized that the change in RNA localization is caused by regionalized zygotic transcription in trout. Regardless of these differing mechanisms, the cross-species comparison revealed a conservation of many transcripts involved in germ cell development and cell proliferation. Moreover, using hybrid trout embryos, we were able to reveal the early onset of de novo transcription. Altogether, these findings indicate how species with large oocytes and prolonged development utilize unique RNA localization strategies. This knowledge expands our understanding of early development across teleost species.
{"title":"RNA redistribution driven by alterations in transcription during early embryogenesis of rainbow trout","authors":"Katerina Cihakova , Ravindra Naraine , Viktoriia Hantzsch , Roman Franek , Martin Psenicka , Radek Sindelka","doi":"10.1016/j.ydbio.2025.11.004","DOIUrl":"10.1016/j.ydbio.2025.11.004","url":null,"abstract":"<div><div>In many species, the differential localization of RNAs along the animal-vegetal axis is established during oogenesis. The resulting asymmetry is essential for axis formation, germ layer patterning, and cell fate determination, especially in fish and amphibians. In recent years, research in this field has focused mainly on zebrafish, which raises the question about the conservation of localization processes across all teleost species. Although extant teleost species utilize meroblastic cleavage only, there are extreme differences in their oocyte size. These differences are fundamentally linked to each species' life history. Some have rapid embryonic development, while embryos of other species, like salmonids, take weeks to develop. This might have consequences on the spatial distribution of biomolecules during oogenesis and their relocalization during early embryogenesis. Yet, our knowledge is based on data from small-sized oocyte species with rapid development only (e.g. zebrafish). In this study, we performed a spatially resolved TOMO-seq method on early embryos of the rainbow trout, a species characterized by prolonged embryonic development and large oocytes, and compared it with zebrafish. We revealed that the maternal pre-patterned localization of transcripts can be disrupted in the early embryo by two main mechanisms: <em>de novo</em> transcription and degradation. The most prominent change can be seen in the emerging blastodisc in the animal pole, where there is a significant increase in localized transcripts. In contrast with research suggesting active relocalization of RNAs by ooplasmic streaming in zebrafish, we hypothesized that the change in RNA localization is caused by regionalized zygotic transcription in trout. Regardless of these differing mechanisms, the cross-species comparison revealed a conservation of many transcripts involved in germ cell development and cell proliferation. Moreover, using hybrid trout embryos, we were able to reveal the early onset of <em>de</em> novo transcription. Altogether, these findings indicate how species with large oocytes and prolonged development utilize unique RNA localization strategies. This knowledge expands our understanding of early development across teleost species.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 21-37"},"PeriodicalIF":2.1,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534023","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 : 2025-11-14DOI: 10.1016/j.ydbio.2025.11.007
Isha Verma , R. Keith Duncan , Haylie L. Miller , Michael Uhler
Developmental biology is one of the fundamental sciences for understanding the basics of life and often intersects with social justice challenges facing society. This article describes an inclusive teaching activity for students and instructors to explore the interface between developmental biology, genetic diversity, and social justice. The instructor and students will choose a recent publication and use it as the basis for exploring the roles of specific genes characterized in autism from educational, emulative, and ethical perspectives. The assignment for students will include a discussion and demonstration of developmental neurobiology and principles of gene function within the nervous system, as well as ethical considerations for how individuals, as well as society as a whole, should consider genetic variations. Two frameworks are introduced for instructors to create an inclusive learning environment, including universal design for learning and multipartiality. Resources and examples are given throughout the article for instructors to use, and a suggested rubric is also provided. A post-activity self-reflection performed by the students will facilitate their own assessment of how the teaching activity has impacted their philosophical and social perspectives on genetic diversity. The short-term goal of the activity is to promote an immediate appreciation of neurodiversity among the participating students, and the long-term goal is to demonstrate the importance of neurodiversity for developing a just society.
{"title":"Teaching developmental neurobiology with inclusion and valuing of neurodivergent learners","authors":"Isha Verma , R. Keith Duncan , Haylie L. Miller , Michael Uhler","doi":"10.1016/j.ydbio.2025.11.007","DOIUrl":"10.1016/j.ydbio.2025.11.007","url":null,"abstract":"<div><div>Developmental biology is one of the fundamental sciences for understanding the basics of life and often intersects with social justice challenges facing society. This article describes an inclusive teaching activity for students and instructors to explore the interface between developmental biology, genetic diversity, and social justice. The instructor and students will choose a recent publication and use it as the basis for exploring the roles of specific genes characterized in autism from educational, emulative, and ethical perspectives. The assignment for students will include a discussion and demonstration of developmental neurobiology and principles of gene function within the nervous system, as well as ethical considerations for how individuals, as well as society as a whole, should consider genetic variations. Two frameworks are introduced for instructors to create an inclusive learning environment, including universal design for learning and multipartiality. Resources and examples are given throughout the article for instructors to use, and a suggested rubric is also provided. A post-activity self-reflection performed by the students will facilitate their own assessment of how the teaching activity has impacted their philosophical and social perspectives on genetic diversity. The short-term goal of the activity is to promote an immediate appreciation of neurodiversity among the participating students, and the long-term goal is to demonstrate the importance of neurodiversity for developing a just society.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"532 ","pages":"Pages 83-100"},"PeriodicalIF":2.1,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534086","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 : 2025-11-13DOI: 10.1016/j.ydbio.2025.11.005
Peter M. Luo , Neha H. Ahuja , Thomas J. Carroll , Ondine Cleaver
During kidney formation, segmented epithelial tubules and blood vessels develop within a heterogeneous and progressively patterned stroma. By E18.5, the murine renal stroma exhibits several transcriptionally and spatially distinct populations, including specialized stromal cells associated with the vasculature, termed mural cells. However, the precise contributions of stromal progenitor lineages to this stromal heterogeneity, as well as the dynamics of renal mural cell investment, remain unclear. Previous studies have described stromal progenitors in the developing cortex that transiently express the transcription factor Foxd1, as well as stromal progenitors in the ureter that express Tbx18, and have shown that both are capable of giving rise to renal stromal cells, including vascular mural cells. Here, we use pulse induction of Tbx19CreERT2 at different timepoints to elucidate the contribution of the Tbx18 population to stromal patterning. We show that the Tbx18-lineage, when induced at E12.5, gives rise to arterial mural cells, without ever progressing through a Foxd1+ cortical stromal progenitor state. These arterial mural cells are only transiently present along arteries during development, ultimately contributing instead to peritubular capillaries. When traced post-natally, the Tbx18-lineage gives rise to pericytes, which are enriched in S3-segment-associated, Cxcl14-enriched stroma in the inner cortex. We show that these pericytes arise directly from arterial mural cells seen earlier during development. These data help clarify a small portion of the complicated lineage relationships of renal stromal progenitors and their contribution to the kidney vascular-associated mural cells.
{"title":"Ureteric stromal progenitors give rise to kidney inner cortical pericytes via an arterial mural cell intermediate","authors":"Peter M. Luo , Neha H. Ahuja , Thomas J. Carroll , Ondine Cleaver","doi":"10.1016/j.ydbio.2025.11.005","DOIUrl":"10.1016/j.ydbio.2025.11.005","url":null,"abstract":"<div><div>During kidney formation, segmented epithelial tubules and blood vessels develop within a heterogeneous and progressively patterned stroma. By E18.5, the murine renal stroma exhibits several transcriptionally and spatially distinct populations, including specialized stromal cells associated with the vasculature, termed mural cells. However, the precise contributions of stromal progenitor lineages to this stromal heterogeneity, as well as the dynamics of renal mural cell investment, remain unclear. Previous studies have described stromal progenitors in the developing cortex that transiently express the transcription factor <em>Foxd1,</em> as well as stromal progenitors in the ureter that express <em>Tbx18</em>, and have shown that both are capable of giving rise to renal stromal cells, including vascular mural cells. Here, we use pulse induction of Tbx19CreERT2 at different timepoints to elucidate the contribution of the <em>Tbx18</em> population to stromal patterning. We show that the <em>Tbx18-</em>lineage, when induced at E12.5, gives rise to arterial mural cells, without ever progressing through a <em>Foxd1+</em> cortical stromal progenitor state. These arterial mural cells are only transiently present along arteries during development, ultimately contributing instead to peritubular capillaries. When traced post-natally, the <em>Tbx18-</em>lineage gives rise to pericytes, which are enriched in S3-segment-associated, <em>Cxcl14</em>-enriched stroma in the inner cortex. We show that these pericytes arise directly from arterial mural cells seen earlier during development. These data help clarify a small portion of the complicated lineage relationships of renal stromal progenitors and their contribution to the kidney vascular-associated mural cells.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 86-101"},"PeriodicalIF":2.1,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530487","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}
Amphibian metamorphosis is tightly regulated by thyroid hormone (TH). During this process, most larval epithelial cells in the Xenopus laevis intestine undergo apoptosis, whereas a small population dedifferentiates into adult epithelial stem cells. They subsequently proliferate and differentiate to form a trough-crest epithelial architecture similar to the mammalian crypt-villus axis. We have previously identified a number of TH-responsive genes likely involved in this intestinal remodeling. Here, we focus on one such gene, folate receptor 4 (folr4). We examined the spatiotemporal expression of folr4.L by using quantitative RT-PCR and in situ hybridization chain reaction (HCR) and found that folr4.L expression is highly upregulated during both natural and TH-induced metamorphosis. Interestingly, in the epithelium at the climax of metamorphosis, folr4.L is specifically expressed in the proliferating and/or differentiating adult epithelial cells located adjacent to proliferating adult stem cells, which express intestinal stem cell marker leucine-rich repeat-containing G protein-coupled 5 (lgr5). Moreover, we identified a TH response element (TRE) in the folr4.L promoter that binds to the heterodimer of TH receptor (TR) and 9-cis retinoic acid receptor (RXR) in vitro and mediates T3-dependent transcriptional activation in vivo. Phylogenetic analysis suggested that X. laevis Folr4.L may be more closely related to riboflavin binding protein (Rfbp) than mammalian FOLR4. These findings suggest that TH-induced Folr4.L might be involved in the development of adult intestinal epithelium.
{"title":"Direct activation of folate receptor 4 by thyroid hormone suggests its role in the development of adult intestinal epithelium during Xenopus laevis metamorphosis","authors":"Kenta Fujimoto , Yuki Shibata , Morihiro Okada , Yun-Bo Shi , Takashi Hasebe","doi":"10.1016/j.ydbio.2025.11.006","DOIUrl":"10.1016/j.ydbio.2025.11.006","url":null,"abstract":"<div><div>Amphibian metamorphosis is tightly regulated by thyroid hormone (TH). During this process, most larval epithelial cells in the <em>Xenopus laevis</em> intestine undergo apoptosis, whereas a small population dedifferentiates into adult epithelial stem cells. They subsequently proliferate and differentiate to form a trough-crest epithelial architecture similar to the mammalian crypt-villus axis. We have previously identified a number of TH-responsive genes likely involved in this intestinal remodeling. Here, we focus on one such gene, <em>folate receptor 4</em> (<em>folr4</em>). We examined the spatiotemporal expression of <em>folr4.L</em> by using quantitative RT-PCR and <em>in situ</em> hybridization chain reaction (HCR) and found that <em>folr4.L</em> expression is highly upregulated during both natural and TH-induced metamorphosis. Interestingly, in the epithelium at the climax of metamorphosis, <em>folr4.L</em> is specifically expressed in the proliferating and/or differentiating adult epithelial cells located adjacent to proliferating adult stem cells, which express intestinal stem cell marker <em>leucine-rich repeat-containing G protein-coupled 5</em> (<em>lgr5</em>). Moreover, we identified a TH response element (TRE) in the <em>folr4.L</em> promoter that binds to the heterodimer of TH receptor (TR) and 9-cis retinoic acid receptor (RXR) <em>in vitro</em> and mediates T3-dependent transcriptional activation <em>in vivo.</em> Phylogenetic analysis suggested that <em>X. laevis</em> Folr4.L may be more closely related to riboflavin binding protein (Rfbp) than mammalian FOLR4. These findings suggest that TH-induced Folr4.L might be involved in the development of adult intestinal epithelium.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"530 ","pages":"Pages 12-20"},"PeriodicalIF":2.1,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523093","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 : 2025-11-10DOI: 10.1016/j.ydbio.2025.11.002
Claire Marie Moran , Irene E. Zohn
The use of time-lapse imaging to study neural tube closure in mouse embryos has provided unexpected insights into the complex morphogenetic processes involved. When neural tube closure is disrupted, it leads to neural tube defects (NTDs), which are among the most common structural birth defects in humans, associated with long-term disabilities and death. This review explores the growing body of research on time-lapse imaging experiments conducted in mice, emphasizing discoveries of the dynamic cellular movements and changes that enable neural tube formation. Advances in mouse embryo culture and live imaging techniques have enabled visualization of dynamic cellular movements and shape changes during neural tube formation, allowing researchers to observe abnormal cell behaviors in genetic mouse models with neural tube closure defects. These studies use transgenic reporters, conditional mouse genetics, and various physical and pharmacological interventions to track tissue and cell behavior and elucidate the underlying molecular and biophysical mechanisms as neural folds rise and fuse at the dorsal midline. Observing neural tube closure in real time has led to important findings, including revealing the crucial role of the surface ectoderm in supporting neural fold elevation and fusion. The coordination of apical constriction with cell cycle progression and apoptosis helps shape the neural plate. Analyzing convergent extension shows that oriented neighbor exchanges—requiring planar cell polarity signaling—drive polarized protrusive activity and actomyosin contractility, along with coordinated apical constriction to elevate and bring the neural folds together. Future innovations are expected to improve the measurement of biomechanical forces during neural tube formation and visualization of deep tissues to clarify mechanisms of cranial mesenchyme morphogenesis during cranial neural fold elevation.
{"title":"Discovering the unexpected: Insights into the dynamics of mouse neural tube closure revealed by time-lapse imaging","authors":"Claire Marie Moran , Irene E. Zohn","doi":"10.1016/j.ydbio.2025.11.002","DOIUrl":"10.1016/j.ydbio.2025.11.002","url":null,"abstract":"<div><div>The use of time-lapse imaging to study neural tube closure in mouse embryos has provided unexpected insights into the complex morphogenetic processes involved. When neural tube closure is disrupted, it leads to neural tube defects (NTDs), which are among the most common structural birth defects in humans, associated with long-term disabilities and death. This review explores the growing body of research on time-lapse imaging experiments conducted in mice, emphasizing discoveries of the dynamic cellular movements and changes that enable neural tube formation. Advances in mouse embryo culture and live imaging techniques have enabled visualization of dynamic cellular movements and shape changes during neural tube formation, allowing researchers to observe abnormal cell behaviors in genetic mouse models with neural tube closure defects. These studies use transgenic reporters, conditional mouse genetics, and various physical and pharmacological interventions to track tissue and cell behavior and elucidate the underlying molecular and biophysical mechanisms as neural folds rise and fuse at the dorsal midline. Observing neural tube closure in real time has led to important findings, including revealing the crucial role of the surface ectoderm in supporting neural fold elevation and fusion. The coordination of apical constriction with cell cycle progression and apoptosis helps shape the neural plate. Analyzing convergent extension shows that oriented neighbor exchanges—requiring planar cell polarity signaling—drive polarized protrusive activity and actomyosin contractility, along with coordinated apical constriction to elevate and bring the neural folds together. Future innovations are expected to improve the measurement of biomechanical forces during neural tube formation and visualization of deep tissues to clarify mechanisms of cranial mesenchyme morphogenesis during cranial neural fold elevation.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 305-319"},"PeriodicalIF":2.1,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502480","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 : 2025-11-08DOI: 10.1016/j.ydbio.2025.11.001
Ziwei Ying , Yizhuang Zhang , Audrey Saquet , Ming Shao , De-Li Shi , Raphaëlle Grifone
The RNA-binding protein Rbm24 is evolutionarily conserved, and its coding gene displays tissue-specific expression in vertebrates. However, the dynamic localization of this protein in different cell lineages remains elusive. We have generated a zebrafish rbm24a-GFP knock-in line in which endogenous Rbm24a is tagged with GFP, allowing the precise monitoring and systematic characterization of its spatiotemporal expression and subcellular localization during development and in the adult. Rbm24a-GFP not only shows strongly restricted expression in a subset of tissues, but also displays cell type- and stage-specific subcellular localization patterns. The protein mainly localizes in the cytoplasm of lens fiber cells and progenitors of sensory hair cells. It undergoes dynamic cytoplasm to nucleus translocation during differentiation of myoblasts and cardiomyoblasts. We further examined the effectiveness of this knock-in line for inhibiting Rbm24a function. Targeted degradation of Rbm24a-GFP using the zGrad system produces phenotypes of zygotic rbm24a mutants or morphants, with defective heart morphogenesis and disrupted cardiac muscle integrity. Therefore, this line will be particularly useful for understanding Rbm24a-GFP dynamic expression and localization changes under homeostasis and pathological conditions. It also enriches the resource of zebrafish knock-in line and provides a convenient tool for functional study of the protein through degron-mediated conditional degradation.
{"title":"A zebrafish rbm24a-GFP knock-in line for monitoring lineage-specific dynamic protein expression and function","authors":"Ziwei Ying , Yizhuang Zhang , Audrey Saquet , Ming Shao , De-Li Shi , Raphaëlle Grifone","doi":"10.1016/j.ydbio.2025.11.001","DOIUrl":"10.1016/j.ydbio.2025.11.001","url":null,"abstract":"<div><div>The RNA-binding protein Rbm24 is evolutionarily conserved, and its coding gene displays tissue-specific expression in vertebrates. However, the dynamic localization of this protein in different cell lineages remains elusive. We have generated a zebrafish <em>rbm24a-GFP</em> knock-in line in which endogenous Rbm24a is tagged with GFP, allowing the precise monitoring and systematic characterization of its spatiotemporal expression and subcellular localization during development and in the adult. Rbm24a-GFP not only shows strongly restricted expression in a subset of tissues, but also displays cell type- and stage-specific subcellular localization patterns. The protein mainly localizes in the cytoplasm of lens fiber cells and progenitors of sensory hair cells. It undergoes dynamic cytoplasm to nucleus translocation during differentiation of myoblasts and cardiomyoblasts. We further examined the effectiveness of this knock-in line for inhibiting Rbm24a function. Targeted degradation of Rbm24a-GFP using the zGrad system produces phenotypes of zygotic <em>rbm24a</em> mutants or morphants, with defective heart morphogenesis and disrupted cardiac muscle integrity. Therefore, this line will be particularly useful for understanding Rbm24a-GFP dynamic expression and localization changes under homeostasis and pathological conditions. It also enriches the resource of zebrafish knock-in line and provides a convenient tool for functional study of the protein through degron-mediated conditional degradation.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"529 ","pages":"Pages 292-304"},"PeriodicalIF":2.1,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488227","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 : 2025-11-06DOI: 10.1016/j.ydbio.2025.10.010
Joana Antonio , Elizabeth Strang , Rom David L. Arca , Matthew H. Sazinsky , Sarah Hasel-Kolossa , Abigail Wiesenthal , Jose Francisco Carranza Celis , Trisha Gongalore , Sagun Bhandari , Sadia Yeasmin , Mihoko Kato
Cell migration is an important process underlying animal embryonic body patterning, organogenesis, and diseases like metastatic cancer. Acetylcholine (ACh) signaling plays a key role in the migration of various cell types and cancer cells, yet in vivo studies are lacking. We investigated the function of nicotinic ACh receptors (nAChRs) on the migration of a gonadal leader cell, the linker cell (LC). During C. elegans male gonadogenesis, the LC migrates posteriorly along the ventral body wall, following a path that runs parallel and adjacent to the ACh-releasing ventral nerve cord (VNC). Excess ACh reoriented the polarity of the LC from posterior-facing to anterior-facing through an intermediate stage of facing the ventral body wall. nAChRs, which are expressed by both the VNC and LC, were required for the LC reversal response. The specific combination of subunits of the pentameric nAChR produced different reversal responses, with acr-16(−) and lgc-9(−) mutants inhibiting and acr-15(−) promoting reversals. LC reversal in response to excess ACh also required the L1 cell adhesion molecule (L1CAM), SAX-7, which is expressed by both VNC and LC. We propose that an increase in ACh signaling in the VNC and LC promotes stronger SAX-7 mediated adhesion of the LC to the ventral body wall, causing the LC to change directions from posterior to ventral facing.
{"title":"Nicotinic acetylcholine receptors function with adhesion molecule SAX-7 to reverse cell orientation during migration","authors":"Joana Antonio , Elizabeth Strang , Rom David L. Arca , Matthew H. Sazinsky , Sarah Hasel-Kolossa , Abigail Wiesenthal , Jose Francisco Carranza Celis , Trisha Gongalore , Sagun Bhandari , Sadia Yeasmin , Mihoko Kato","doi":"10.1016/j.ydbio.2025.10.010","DOIUrl":"10.1016/j.ydbio.2025.10.010","url":null,"abstract":"<div><div>Cell migration is an important process underlying animal embryonic body patterning, organogenesis, and diseases like metastatic cancer. Acetylcholine (ACh) signaling plays a key role in the migration of various cell types and cancer cells, yet <em>in vivo</em> studies are lacking. We investigated the function of nicotinic ACh receptors (nAChRs) on the migration of a gonadal leader cell, the linker cell (LC). During <em>C. elegans</em> male gonadogenesis, the LC migrates posteriorly along the ventral body wall, following a path that runs parallel and adjacent to the ACh-releasing ventral nerve cord (VNC). Excess ACh reoriented the polarity of the LC from posterior-facing to anterior-facing through an intermediate stage of facing the ventral body wall. nAChRs, which are expressed by both the VNC and LC, were required for the LC reversal response. The specific combination of subunits of the pentameric nAChR produced different reversal responses, with <em>acr-16(−)</em> and <em>lgc-9</em>(−) mutants inhibiting and <em>acr-15</em>(−) promoting reversals. LC reversal in response to excess ACh also required the L1 cell adhesion molecule (L1CAM), SAX-7, which is expressed by both VNC and LC. We propose that an increase in ACh signaling in the VNC and LC promotes stronger SAX-7 mediated adhesion of the LC to the ventral body wall, causing the LC to change directions from posterior to ventral facing.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":"531 ","pages":"Pages 45-55"},"PeriodicalIF":2.1,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476675","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号