DevelopmentPub Date : 2025-07-15Epub Date: 2025-07-18DOI: 10.1242/dev.205069
Gabriel E Valdebenito, Margarete Diaz-Cuadros
{"title":"In preprints: setting the tempo of development.","authors":"Gabriel E Valdebenito, Margarete Diaz-Cuadros","doi":"10.1242/dev.205069","DOIUrl":"https://doi.org/10.1242/dev.205069","url":null,"abstract":"","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 14","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658712","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 : 2025-07-15Epub Date: 2025-07-18DOI: 10.1242/dev.204626
Jaehwan Kim, Chad S Driscoll, Lijia Li, Catherine A Wilson, Wei Xie, Jason G Knott
{"title":"Deciphering the role of cis-regulatory elements and TFAP2C in the activation of zygotic Sox2 expression in mouse preimplantation embryos.","authors":"Jaehwan Kim, Chad S Driscoll, Lijia Li, Catherine A Wilson, Wei Xie, Jason G Knott","doi":"10.1242/dev.204626","DOIUrl":"10.1242/dev.204626","url":null,"abstract":"<p><p>Cell fate decisions in preimplantation embryos require the coordinated expression of pluripotency and lineage-specific transcription factors. SOX2 represents the first pluripotency regulator for which expression is restricted to the inside cells of mouse preimplantation embryos. However, the genetic mechanisms that activate the expression of zygotic Sox2 are poorly understood. Here, we report that Sox2 expression in mouse embryos is controlled by the actions of key cis-regulatory elements, including a proximal promoter and super enhancer. We show that TFAP2C, a key trophoblast lineage regulator, binds to the Sox2 proximal promoter to activate its expression. Lastly, we provide evidence that TFAP2C and the HIPPO signaling pathway cooperatively regulate Sox2 expression. In summary, this work has important implications for understanding how conventional trophoblast transcription factors, such as TFAP2C, contribute to the activation of early pluripotency genes to facilitate divergent cellular states that support lineage formation.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12338974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"H3K36me3 modification by SETD2 is essential for Col11a2 and Sema3e transcription to maintain dentinogenesis in mice.","authors":"Jiaxin Niu, Jing Fu, Hao Feng, Jiahao Han, Zhi Chen, Guobin Yang, Guohua Yuan","doi":"10.1242/dev.204352","DOIUrl":"10.1242/dev.204352","url":null,"abstract":"<p><p>Dentin is a major mineralized component of teeth generated by odontoblasts. Several types of histone methylation have been reported to play important roles in odontoblast differentiation and dentinogenesis. However, the role of methylation on histone 3 at lysine 36 (H3K36) remains enigmatic. Here, we demonstrate high expression of SETD2, a methyltransferase catalyzing the trimethylation of H3K36 (H3K36me3), in the odontoblast layer. In vitro knockdown experiments and in vivo observations of two conditional knockout mouse models reveal that SETD2 is essential for odontoblast differentiation and dentinogenesis. Integrated analyses of RNA sequencing and spike-in CUT&Tag sequencing data show that SETD2 is crucial for both H3K36me3 occupancy at the loci of Col11a2 and Sema3e and their transcription. Further experiments verify that COL11A2 and SEMA3E act upstream of AKT1 signaling, promoting odontoblastic differentiation. In vitro and in vivo activation of AKT1 using SC79 (an AKT activator) partially rescues the impaired odontoblast differentiation caused by Setd2 knockdown or deficiency. Therefore, our findings indicate that H3K36me3 mediated by SETD2 is essential for dentinogenesis by regulating the expression of Col11a2 and Sema3e and AKT1 signaling.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12338916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DevelopmentPub Date : 2025-07-15Epub Date: 2025-07-31DOI: 10.1242/dev.204662
Bénédicte M Lefèvre, Marine Delvigne, Aurélie Camprodon, Josué Vidal, Virginie Courtier-Orgogozo, Michael Lang
{"title":"Evolution of a novel left-right asymmetry in organ size by co-option of a tissue rotation process.","authors":"Bénédicte M Lefèvre, Marine Delvigne, Aurélie Camprodon, Josué Vidal, Virginie Courtier-Orgogozo, Michael Lang","doi":"10.1242/dev.204662","DOIUrl":"10.1242/dev.204662","url":null,"abstract":"<p><p>Left-right asymmetries have repeatedly evolved in diverse animals and affect the position, shape or size of specific organs. How novel left-right asymmetries arise remains unknown. Here, we examined Drosophila pachea, where males have evolved unique asymmetric genitalia lobes and a right-sided copulation posture in the past 3-6 million years. We found that male asymmetric lobes grow in pupae during a 360° clockwise genitalia rotation, which is a conserved and widespread developmental process in flies. Using two complementary approaches, drug application and a CRISPR-induced myo1D mutant, we altered genitalia rotation and found that asymmetric lobe sizes depend on genitalia rotation completion, while the sidedness of lobe asymmetry is determined by the rotation direction. We then investigated the impact of genital asymmetry on copulation posture. Males with reversed genital asymmetry still mate in the typical right-sided posture, indicating that right-sided behavior is not determined by asymmetric male genitalia. Our study reveals that a novel genitalia asymmetry has evolved through the co-option of a pre-existing tissue remodeling process. Tissue rotation represents a previously unreported mechanism, through which a bilateral organ can acquire a left-right size asymmetry.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539475","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 : 2025-07-15Epub Date: 2025-07-31DOI: 10.1242/dev.205090
{"title":"The people behind the papers - Bénédicte Marie Lefèvre and Michael Lang.","authors":"","doi":"10.1242/dev.205090","DOIUrl":"https://doi.org/10.1242/dev.205090","url":null,"abstract":"<p><p>Bilaterians with overall left-right symmetric external bodies often have internal organs that display left-right asymmetry. In a new study, Michael Lang and colleagues study the male genitalia of Drosophila pachea to investigate how left-right asymmetry could have evolved de novo. They find that male genital lobe asymmetry has evolved through the co-option of an existing developmental process - genitalia tissue rotation. To find out more about this work, we caught up with first author Bénédicte Marie Lefèvre and corresponding author Michael Lang, CNRS researcher at the Laboratoire - Evolution, Génomes, Comportement, Ecologie (EGCE).</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 14","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752677","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}
{"title":"Caenorhabditis elegans LET-381 and DMD-4 control development of the mesodermal HMC endothelial cell.","authors":"Nikolaos Stefanakis, Jasmine Xi, Jessica Jiang, Shai Shaham","doi":"10.1242/dev.204622","DOIUrl":"10.1242/dev.204622","url":null,"abstract":"<p><p>Endothelial cells form the inner layer of blood vessels and play key roles in circulatory system development and function. A variety of endothelial cell types have been described through gene expression and transcriptome studies; nonetheless, the transcriptional programs that specify endothelial cell fate and maintenance are not well understood. To uncover such regulatory programs, we studied the C. elegans head mesodermal cell (HMC), a non-contractile mesodermal cell bearing molecular and functional similarities to vertebrate endothelial cells. Here, we demonstrate that a Forkhead transcription factor, LET-381, is required for HMC fate specification and maintenance of HMC gene expression. DMD-4, a DMRT transcription factor, acts downstream of and in conjunction with LET-381 to mediate these functions. Independently of LET-381, DMD-4 also represses the expression of genes associated with a different, non-HMC, mesodermal fate. Our studies uncover essential roles for FoxF transcriptional regulators in endothelial cell development and suggest that FoxF co-functioning target transcription factors promote specific non-contractile mesodermal fates.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 14","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of klf2 in innovation of the Pmar1-HesC double-negative gate in echinoderms.","authors":"Nina Levin, Natalia Gogoleva, Atsuko Yamazaki, Shumpei Yamakawa, Yoshiaki Morino, Hiroshi Wada","doi":"10.1242/dev.204492","DOIUrl":"10.1242/dev.204492","url":null,"abstract":"<p><p>The diversity of organism morphology is heavily dependent on the evolution of gene regulatory networks. However, the mechanistic basis on which change can be incorporated within these systems remains poorly understood. Evolution of the echinoderm hesC gene as a novel upstream mesoderm regulator found uniquely in the euechinoid sea urchin lineage is an intriguing example of gene regulatory network modification. To reveal how new components can be incorporated within upstream pathways, we investigated the starfish mesoderm regulatory pathway, which lacks the derived hesC mesoderm regulation. We show that starfish HesC is able to perform the function of endogenous HesC in the context of sea urchin embryogenesis. Furthermore, we revealed that both starfish and euechinoids employ the klf2 gene as an upstream mesoderm regulator within a similar regulatory apparatus as the euechinoid hesC. It can be speculated that klf2 plays a crucial role in buffering the recruitment of hesC into a similar regulatory position through a gradual exchange of players, which may be a prevalent mechanism for drastic regulatory innovations.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483601","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 : 2025-07-15Epub Date: 2025-07-28DOI: 10.1242/dev.204596
Diana Wichmann Graff, Emilie Liv Bang-Jensen, Anuska la Rosa Egeskov-Madsen, Palle Serup, Philip A Seymour
{"title":"Fbxw7 regulates N1ICD and Sox9 perdurance during pancreas development to ensure proper cell lineage allocation and segregation.","authors":"Diana Wichmann Graff, Emilie Liv Bang-Jensen, Anuska la Rosa Egeskov-Madsen, Palle Serup, Philip A Seymour","doi":"10.1242/dev.204596","DOIUrl":"10.1242/dev.204596","url":null,"abstract":"<p><p>In the developing mouse pancreas, Notch signaling first maintains multipotent pancreatic progenitor cells (MPCs), suppressing early endocrine differentiation, then promotes their adoption of a duct/endocrine-bipotent progenitor (BP) fate at the expense of Notch-independent pro-acinar progenitors (PACs). Active Notch signaling is terminated by Notch intracellular domain (NICD) degradation via the E3 ubiquitin ligase SCFFbxw7, which also regulates the stability of other unidentified substrates in developing pancreas. We show here that endodermal deletion of the substrate recognition component Fbxw7 dose-dependently suppresses early endocrine differentiation, which is consistent with Notch1 ICD (N1ICD) upregulation in MPCs, then perturbs later acinar and ductal morphogenesis. PACs of Fbxw7 mouse mutants ectopically express Sox9 and N1ICD, which is associated with defective acinar differentiation, while their ducts are cystic with intermingled endocrine cells and inappropriate external openings. While genetic blockade of Notch transduction normalizes early endocrine differentiation in Fbxw7 mouse mutants, it is unable to rescue the later acinar phenotype, which, instead, can be normalized by Sox9 haploinsufficiency. Fbxw7 is thus required to limit N1ICD and Sox9 perdurance in the developing pancreas to enable appropriate early endocrine differentiation and to allow the complete segregation of BP and PAC lineages.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539476","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 : 2025-07-15Epub Date: 2025-07-29DOI: 10.1242/dev.204317
Haley E Brown, Claude Jean-Guillaume, Brandon P Weasner, Justin P Kumar
{"title":"Differential regulation of eye specification in Drosophila by Polycomb Group epigenetic repressors.","authors":"Haley E Brown, Claude Jean-Guillaume, Brandon P Weasner, Justin P Kumar","doi":"10.1242/dev.204317","DOIUrl":"10.1242/dev.204317","url":null,"abstract":"<p><p>During metazoan development, chromatin plasticity and genetic regulation are tightly connected to establish proper tissue fate and patterning. Drosophila imaginal discs are excellent models to study these processes as both genetic and mechanical injury can redirect their fate during regeneration. Reducing expression of Polycomb (Pc) results in the ectopic activation of the wing selector gene vestigial (vg) which in turn interacts with its DNA-binding partner Scalloped (Sd) - this forces the eye to transform into a wing. Reductions of other Polycomb Group members alone do not phenocopy this transformation. However, knocking down Sex comb on midleg (Scm) or Scm-related gene containing four mbt domains (Sfmbt) alongside the Pax6 gene twin of eyeless (toy) enables the eye-to-wing transformation. Using high throughput sequencing we show that toy-Sfmbt and toy-Scm knockdowns alter expression of both wing selector and Hox genes. These findings provide new insights into how the fate of the eye is specified.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}