DevelopmentPub Date : 2025-10-01Epub Date: 2025-09-30DOI: 10.1242/dev.205224
Chee Kiang Ewe, Max S Farnworth, Anzy Miller, Joaquín Navajas Acedo, Marlies E Oomen, Giulia Paci, Sonya A Widen, Toshimichi Yamada
{"title":"Pathway to Independence: a forecast for the future of developmental biology.","authors":"Chee Kiang Ewe, Max S Farnworth, Anzy Miller, Joaquín Navajas Acedo, Marlies E Oomen, Giulia Paci, Sonya A Widen, Toshimichi Yamada","doi":"10.1242/dev.205224","DOIUrl":"https://doi.org/10.1242/dev.205224","url":null,"abstract":"<p><p>In 2022, Development launched its Pathway to Independence (PI) programme, aimed at supporting postdocs as they transition to their first independent position. In 2025, we welcome our third cohort of eight talented PI fellows. In this article, each fellow discusses their perspective on the future of their field and how their work will contribute to this exciting new era.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 19","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-10-01Epub Date: 2025-10-06DOI: 10.1242/dev.204425
Isidora Rovic, Katherine Szelag, Han Li, Rosanne McQuaid, Sara Sugin, Que Wu, Natalia Theodora, John Sled, Andrea Jurisicova
{"title":"Acid sphingomyelinase is a gatekeeper of placental labyrinthine architecture and function.","authors":"Isidora Rovic, Katherine Szelag, Han Li, Rosanne McQuaid, Sara Sugin, Que Wu, Natalia Theodora, John Sled, Andrea Jurisicova","doi":"10.1242/dev.204425","DOIUrl":"10.1242/dev.204425","url":null,"abstract":"<p><p>Sphingolipids are a class of bioactive signaling lipids that regulate an array of fundamental cellular processes, including cell survival, proliferation and differentiation. Deficiency of acid sphingomyelinase - an enzyme of the sphingolipid metabolic pathway - has been previously implicated in human placental pathologies. We demonstrate that acid sphingomyelinase (Smpd1) is required for normal placental development in the mouse, and its deficiency results in an intrauterine growth restriction phenotype. Smpd1-deficient placentas display several anatomical abnormalities, including a reduced labyrinth compartment and increased fetal-maternal interhaemal distance. Finally, we observed several hallmarks of defective autophagy and lysosomal impairment in Smpd1-/- placentas, which could explain the inability of Smpd1-/- trophoblast to respond to nutrient starvation. Fetal growth restriction could not be rescued by transfer of Smpd1-deficient embryos into a wild-type uterine environment; however, restoration of transcription factor EB phosphorylation was detected. Thus, we conclude that, due to a smaller labyrinthine area, Smpd1 deficiency leads to a decrease in exchange between maternal and fetal blood space, limiting the supply of nutrients to the fetus and resulting in growth restriction.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-10-01Epub Date: 2025-10-09DOI: 10.1242/dev.204821
Kalki Kukreja, Allon Klein
{"title":"Coupling and decoupling of the cell cycle from cell differentiation in development.","authors":"Kalki Kukreja, Allon Klein","doi":"10.1242/dev.204821","DOIUrl":"https://doi.org/10.1242/dev.204821","url":null,"abstract":"<p><p>For over a century, biologists have examined how the cell cycle and differentiation influence one another. While it is well established that cell fate decisions can regulate the cell cycle, the reciprocal effect of the cycle on differentiation remains more contentious. Here, we review mechanisms by which cell cycle events can influence differentiation in animals, but focus primarily on the widespread evidence that these processes are often uncoupled. Erythropoiesis provides a rare example where S-phase progression appears to be strictly required for a key commitment step across different species, whereas many other tissues differentiate normally despite complete arrest of cell division. We propose that decoupling cell cycle progression from differentiation enables independent control of tissue size and cell size and allows the cell cycle to tune progenitor numbers in response to physiological and evolutionary demands. Advances in single-cell and spatial transcriptomics now allow systematic assessment of coupling across tissues and developmental stages, and can disentangle genuine dependencies from stress responses induced by classical cell cycle inhibitors. Division and differentiation interact through multiple molecular pathways, but buffering these interactions to maintain weak or no coupling may be essential for adapting developmental processes.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 19","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-10-01Epub Date: 2025-10-14DOI: 10.1242/dev.204963
Beth A Firulli, Chloe A Ferguson, Corrie de Gier-de Vries, Ram Podicheti, Douglas B Rusch, Vincent M Christoffels, Michael Rubart-von der Lohe, Anthony B Firulli
{"title":"Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects.","authors":"Beth A Firulli, Chloe A Ferguson, Corrie de Gier-de Vries, Ram Podicheti, Douglas B Rusch, Vincent M Christoffels, Michael Rubart-von der Lohe, Anthony B Firulli","doi":"10.1242/dev.204963","DOIUrl":"10.1242/dev.204963","url":null,"abstract":"<p><p>The bHLH transcription factors HAND1 and HAND2 are expressed in partially overlapping patterns during development. Studies have established evidence for significant functional redundancy between HAND1 and HAND2. To test redundancy fully, we engineered a Hand1 allele in which we directly replaced the Hand1 exons and intron with those of Hand2. The results show that 2% of Hand1Hand2/Hand2 mice are viable and fertile. The remaining Hand1Hand2/Hand2 embryos exhibit neonatal lethality due to omphalocele accompanied by ventricular septal defects and conduction anomalies. Omphalocele can occur due to altered gut rotation. Our transcriptomic expression analysis reveals that established gene expression patterns associated with normal gut rotation are compromised. Interrogation of cardiac function in surviving Hand1Hand2/Hand2 mice reveals QRS abnormalities and cardiac morphogenic defects. These data support previous findings that HAND factors exhibit extensive functional overlap but also reveals that HAND1 protein has unique functions within the Hand1 expression domain and is required for normal embryonic development.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-10-01Epub Date: 2025-10-13DOI: 10.1242/dev.205051
Olga Kyrchanova, Ksenia Kudryashova, Airat Ibragimov, Vasilisa Dubrovskaya, Paul Schedl, Pavel Georgiev
{"title":"Embryonic enhancers help transmit positional information to the initiator cores that control Drosophila Abd-B regulatory domains.","authors":"Olga Kyrchanova, Ksenia Kudryashova, Airat Ibragimov, Vasilisa Dubrovskaya, Paul Schedl, Pavel Georgiev","doi":"10.1242/dev.205051","DOIUrl":"10.1242/dev.205051","url":null,"abstract":"<p><p>Drosophila homeotic gene Abdominal-B (Abd-B) is controlled throughout development by four infraabdominal (iab) regulatory domains, the active or repressed state of which is determined by initiators that have parasegment-specific enhancer activity at an early stage of embryonic development. For this reason, it has long been assumed that the enhancer activity and initiation function of these elements are synonymous. Here, we studied two initiators that regulate the activity of the iab-5 and iab-6 domains responsible for Abd-B expression in embryonic parasegment PS10 (adult segment A5) and PS11(A6), respectively. In both initiators, core regions were identified that do not stimulate reporter gene transcription, but retain the ability to establish the appropriate activity state of the corresponding iab domains. Other initiator sequences are responsible for parasegment-specific reporter activation in early embryos and enhance the activity of the core initiators. Taken together, our results indicate that initiators represent a new type of regulatory element that function as on/off switches for regulatory domains controlling segment-specific Abd-B expression during Drosophila development.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-10-01Epub Date: 2025-10-13DOI: 10.1242/dev.204875
Madrikha D Saturne, Susan M Motch Perrine, Qingyang Li, Joan T Richtsmeier, Ethylin Wang Jabs, Harm van Bakel, Greg Holmes
{"title":"Differential regulation of coronal and lambdoid suture patency by PTHLH and HHIP activity in mice.","authors":"Madrikha D Saturne, Susan M Motch Perrine, Qingyang Li, Joan T Richtsmeier, Ethylin Wang Jabs, Harm van Bakel, Greg Holmes","doi":"10.1242/dev.204875","DOIUrl":"10.1242/dev.204875","url":null,"abstract":"<p><p>Craniofacial development depends on the formation of fibrous joints, or sutures, between skull bones. Premature fusion of sutures, or craniosynostosis, is a common human pathology. Ectopic Hedgehog (HH) signaling is one cause of craniosynostosis. Hhip encodes an inhibitor of HH ligands, and we previously identified coronal suture dysgenesis in embryonic Hhip-/- mice, in which suture mesenchyme was depleted between closely opposed but unfused osteogenic fronts at E18.5. Here, we report that the lambdoid suture fuses in Hhip-/- mice by E18.5. RNA-seq analysis of the Hhip-/- coronal and lambdoid sutures show that HH target gene expression, including Pthlh, is upregulated. Paradoxically, expression of Ihh is downregulated. We hypothesized that PTHLH, a negative regulator of Ihh expression, may reduce HH signaling to promote coronal suture patency and prevent fusion of the Hhip-/- coronal suture. We generated Hhip-/-;Pthlh-/- embryos and found that coronal sutures are fusing by E18.5. Our results reveal a previously undescribed role for Pthlh in suture development and demonstrate suture-specific roles for HH inhibitors in maintaining suture patency.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-10-01Epub Date: 2025-10-10DOI: 10.1242/dev.204868
Gabrielle C Audu, Sally Y Rohan, Archana Kumari
{"title":"Gas1 regulates embryonic tongue muscle proliferation, differentiation and maturation via alternative pathways to Hedgehog signaling.","authors":"Gabrielle C Audu, Sally Y Rohan, Archana Kumari","doi":"10.1242/dev.204868","DOIUrl":"10.1242/dev.204868","url":null,"abstract":"<p><p>Hedgehog (HH) signaling supports tongue and taste organ development. While the tongue is highly muscular, the role of HH signaling in muscle growth remains poorly understood. We recently showed the expression of HH receptor Gas1 in postnatal lingual muscle. To understand the role of Gas1 in the embryonic tongue, we first examined its expression using Gas1lacZ mouse and GAS1 immunostaining. Our results reveal parallel gene and protein expression in epithelial taste buds, stroma and muscles. We assessed Gas1 constitutive and muscle-specific conditional (E12.5-E18.5) gene deletion effects at E18.5. Constitutive Gas1 deletion disrupts myoblast count, cell proliferation, differentiation, maturation and motor structures, and differentially affects the size and number of intrinsic tongue muscles. We unmask the expression of other HH co-receptors, CDON and BOC, in lingual epithelium, stroma or muscles, which, along with HH-responding GLI1 cells, persists, despite Gas1 deletion. We propose an interplay of Gas1 in distinct lingual compartments for tongue myogenesis, which is independent of HH signaling. We also suggest that while the cell-intrinsic roles of Gas1 in muscle development may be redundant with other HH co-receptors, its cross-compartmental function is not.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-10-01Epub Date: 2025-10-08DOI: 10.1242/dev.205264
Gat Rauner, Nicole C Traugh, Colin J Trepicchio, Meadow E Parrish, Kenan Mushayandebvu, Charlotte Kuperwasser
{"title":"Correction: Single-cell organogenesis captures complex breast tissue formation in three dimensions.","authors":"Gat Rauner, Nicole C Traugh, Colin J Trepicchio, Meadow E Parrish, Kenan Mushayandebvu, Charlotte Kuperwasser","doi":"10.1242/dev.205264","DOIUrl":"https://doi.org/10.1242/dev.205264","url":null,"abstract":"","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 20","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-10-01Epub Date: 2025-10-10DOI: 10.1242/dev.204873
Vanessa Gonzalez, Meagan G Grant, Makoto Suzuki, Briana Christophers, Jessica Rowland Williams, Rebecca D Burdine
{"title":"Synergistic and independent roles for Nodal and FGF in zebrafish cardiac progenitor cell migration and asymmetric heart morphogenesis.","authors":"Vanessa Gonzalez, Meagan G Grant, Makoto Suzuki, Briana Christophers, Jessica Rowland Williams, Rebecca D Burdine","doi":"10.1242/dev.204873","DOIUrl":"10.1242/dev.204873","url":null,"abstract":"<p><p>Asymmetric development of the vertebrate heart is driven by a complex sequence of morphogenetic cell movements, coordinated through precise interpretation of signaling cues by the heart primordia. Here, we show that Nodal signaling functions synergistically with FGF to stimulate the migration of cardiac progenitor cells (CPCs) during cardiac jogging - the first morphological asymmetry observed in zebrafish heart development. While Nodal directs the asymmetric migration of CPCs, we find FGF signaling to be dispensable for this asymmetry, suggesting that FGF plays a permissive rather than instructive role. We further demonstrate that Nodal signaling induces asymmetries in actin cytoskeletal dynamics that correlate with the directional migration of CPCs, whereas FGF does not influence this actin asymmetry. In addition to influencing jogging, FGF and Nodal synergize to ensure proper heart looping. We also provide evidence that FGF contributes to heart looping by promoting the differentiation of the second heart field. Together, these findings offer insight into how the spatiotemporal dynamics of signaling pathways regulate the cellular behaviors driving organ morphogenesis.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-10-01Epub Date: 2025-10-13DOI: 10.1242/dev.205281
{"title":"The people behind the papers - Ksenia Kudryashova and Olga Kyrchanova.","authors":"","doi":"10.1242/dev.205281","DOIUrl":"https://doi.org/10.1242/dev.205281","url":null,"abstract":"<p><p>Hox genes, such as Drosophila Abdominal-B (Abd-B), regulate the morphogenesis of specific anatomical regions along the anteroposterior axis in vertebrates. In their work, Olga Kyrchanova and colleagues find that specific initiator sequences control the activity states of the regulatory domains that direct Abd-B expression in the designated segments during Drosophila development. To know more about their work, we spoke to Ksenia Kudryashova and the corresponding author, Olga Kyrchanova, Group Leader, Institute of Gene Biology, Russian Academy of Sciences, Russia.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 19","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}