Development
· 2026 Feb · PMID 41718037
·
Full text
The neural crest is a vertebrate stem cell population with broad developmental potential. While a gene regulatory network describing establishment of these cells has been generated, much remains to be learned about the d...The neural crest is a vertebrate stem cell population with broad developmental potential. While a gene regulatory network describing establishment of these cells has been generated, much remains to be learned about the dynamics of this process. Here, we use fluorescent in situ hybridization chain reaction to quantify the spatiotemporal dynamics of neural crest formation in Xenopus. We find that the initial onset of neural crest genes is broad and partially overlapping, with distinct anterior-posterior and medio-lateral biases. A shared neural crest domain emerges, but some genes retain relative expression differences that persist into migratory stages, producing stream-specific gene expression patterns. These differences correlate with dynamic expression of the neural plate border factors pax3 and zic1. Correlating relative intensities of pax3 and zic1 with the presence or absence of nascent neural crest transcripts predicts that these factors can differentially regulate snai2 and sox8, which we confirm experimentally. Strikingly, later stages display an inverse correlation between neural crest and neural plate border factors, suggesting that pax3 and zic1 initially promote neural crest gene activation but are downregulated as neural crest identity emerges.
Development
· 2026 Feb · PMID 41649345
·
Publisher ↗
Microtia is a common feature of several human syndromes affecting the external ear (pinna), yet the cellular and molecular mechanisms remain poorly understood. Using human embryos and mouse models of branchio-oto-renal (...Microtia is a common feature of several human syndromes affecting the external ear (pinna), yet the cellular and molecular mechanisms remain poorly understood. Using human embryos and mouse models of branchio-oto-renal (BOR) and 22q11.2 deletion syndromes, we show that the syndromic genes Eya1 and Tbx1 are expressed in mesoderm-derived auricular muscle. In Eya1 mutant mice, auricular muscles failed to form and pinna morphogenesis was disrupted, with comparable defects observed in mesoderm-specific Tbx1 mutants. Both mutant pinnae exhibited impaired cartilage differentiation, suggesting that auricular muscle provides signals to the neural crest-derived mesenchyme to regulate cartilage differentiation. In contrast, defects in cartilage development alone or loss of muscle contraction did not affect early pinna morphogenesis. Auricular myocytes expressed Fgfs, while the surrounding mesenchyme expressed Fgfr1, Fgfr2 and ERM proteins. Disrupted Fgf signalling was observed in mutant cartilage and muscle. In ex vivo cultures, inhibition of Fgf or Bmp signalling recapitulated cartilage defects, whereas BMP4 restored Sox9 expression. These findings identify the mesoderm as essential for pinna initiation and morphogenesis, and reveal signalling mechanisms underlying microtia in BOR and 22q11.2 deletion syndromes.
Aleman AG, Ulloa B, Nayak R
… +10 more, Ford C, Potts KS, de Sena-Tomás C, Vicioso C, Rangaswamy U, Elias HK, Kharas MG, Sanges R, Bowman T, Targoff KL
Development
· 2026 Feb · PMID 41601327
·
Full text
Hematopoietic stem and progenitor cells (HSPCs) have multilineage potential and sustain long-term self-renewal. Deriving patient-specific HSPCs has immense therapeutic potential to overcome the shortage of compatible don...Hematopoietic stem and progenitor cells (HSPCs) have multilineage potential and sustain long-term self-renewal. Deriving patient-specific HSPCs has immense therapeutic potential to overcome the shortage of compatible donors for transplantation. In zebrafish, hemogenic endothelium (HE) is a specialized collection of dorsal aortic endothelial cells (ECs) that give rise to HSPCs. Our data reveal that Cysteine rich intestinal protein 2 (Crip2) has a previously unrecognized function in establishing the proper EC environment for HSPC specification. To investigate the requirement of Crip2, we generated loss-of-function alleles in crip2 and crip3, a gene family member with cardiovascular expression. crip2-/-;crip3-/- (cripDM) embryos exhibit decreased HSPC emergence with impaired lineage derivative production. Single cell RNA-sequencing of kdrl:mCherry+ ECs reveals upregulation of vascular development signature and failure to repress Notch signals during the vital transition of HE specification to HSPC emergence. Moreover, our data underscore that inhibition of Notch promotes HSPC generation in cripDM embryos and Crip genes operate through NF-κB to limit Notch. Identification of Crip2 as a novel regulator of Notch repression in HE will enhance our understanding of cues necessary to improve human HSPC production in vitro.
Subramanian A, Nayak PK, Miller CL
… +4 more, Dranow DB, Roberts RR, Crump JG, Schilling TF
Development
· 2026 Jan · PMID 41582829
·
Full text
Tenocytes secrete the extracellular matrix (ECM) of tendons and ligaments in response to mechanical forces from the muscles and bones to which they attach. Although these tissues are often injured and weaken with age, we...Tenocytes secrete the extracellular matrix (ECM) of tendons and ligaments in response to mechanical forces from the muscles and bones to which they attach. Although these tissues are often injured and weaken with age, we know little about the genetic mechanisms controlling their development or maintenance. Through single-cell RNA sequencing (scRNA-seq) of connective tissues in the embryonic zebrafish head, we identify distinct subpopulations of developing tenocytes and ligamentocytes. Spatially distinct transcriptional cell signatures, particularly for ECM genes, correlate with the type of tendon/ligament (i.e. longer load-bearing skeletal attachments versus soft tissue attachments) as well as tenocyte locations within tendons (i.e. skeletal entheses versus myotendinous junctions). Combinatorial in situ analyses confirm spatial co-expression of genes defining many of these subsets of tendon or ligament cells. From pathway analysis, the scRNA-seq data also suggest a role for canonical Wnt signaling in tenocyte development. Genetic and pharmacological Wnt manipulations alter tenocyte aggregation and cause ectopic cranial muscle attachments. These findings reveal previously unappreciated spatial and functional heterogeneity in tenocytes during embryogenesis and define a role for Wnt signaling in attachment patterning and morphogenesis.
Udayakumar A, Stavropoulos F, Hadjipanteli T
… +11 more, Peng G, Bahuguna S, MacClay C, Lee JY, Xiao Q, Xia Y, Boutros M, Zhou J, Apidianakis Y, Pitsouli C, Ligoxygakis P
Development
· 2026 Jan · PMID 41552968
·
Full text
The intestinal interphase is where epithelial renewal and tissue maintenance are balanced alongside immunological regulation. How these functions integrate with cellular signalling is under investigation. Here, we studie...The intestinal interphase is where epithelial renewal and tissue maintenance are balanced alongside immunological regulation. How these functions integrate with cellular signalling is under investigation. Here, we studied the role of the evolutionarily conserved innate immune Toll/NF-κB pathway in Drosophila intestinal regeneration. We found that the core components of the canonical Toll pathway were necessary for intestinal stem cell (ISC) mitosis in homeostasis and upon infection. Toll activation was sufficient to push ISCs into mitosis and the enteroblast (EB) fate, but blocked EB differentiation resulting in ISC and EB accumulation. This was mediated by JNK and Akt/TOR signalling. When JNKK, JNK, Akt or TOR activity was reduced in gut progenitors, ISC mitosis was suppressed. Toll activation also triggered suppression of antimicrobial lysozyme and amidase genes, which led to increased gut bacterial density. Our results identify Toll as necessary and sufficient for ISC mitosis. Our model is that the Toll pathway acts as a regulator of the intestinal landscape integrating JNK and Akt signals to achieve gut tissue renewal and control of commensal bacteria density.
Development
· 2026 Jan · PMID 41524700
·
Publisher ↗
MEIOC, which is part of an RNA-binding complex, regulates meiosis-associated genes through STRA8-MEIOSIN during spermatogenesis. In their work, Maria Mikedis and colleagues show that MEIOC initiates the mitosis-to-meiosi...MEIOC, which is part of an RNA-binding complex, regulates meiosis-associated genes through STRA8-MEIOSIN during spermatogenesis. In their work, Maria Mikedis and colleagues show that MEIOC initiates the mitosis-to-meiosis transition in mammalian oocytes by repressing the mitotic cyclin CCNA2 and promoting the STRA8-MEIOSIN pathway. To learn about their work, we spoke to the first author, Esther Ushuhuda, and the corresponding author, Maria Mikedis, Assistant Professor, UC Department of Pediatrics, Cincinnati Children's Hospital, USA.
Development
· 2026 Jan · PMID 41521804
·
Full text
Frank-ter Haar syndrome (FTHS) is an inherited disease associated with variants of the SH3PXD2B gene, encoding for the podosomal adaptor protein known as TKS4. FTHS is characterized by multiple skeletal abnormalities, de...Frank-ter Haar syndrome (FTHS) is an inherited disease associated with variants of the SH3PXD2B gene, encoding for the podosomal adaptor protein known as TKS4. FTHS is characterized by multiple skeletal abnormalities, developmental delay and severe craniofacial dysmorphology. This study provides an in-depth characterization of the calvarial phenotype of a mouse model of FTHS and investigates the potential underlying molecular and transcriptomic mechanisms. The Sh3Pxd2bnee-/- mouse presents with craniofacial malformations and disrupted suture patterning, as well as reduced osteoregeneration and decreased cell proliferation and migration observed both in vitro and in vivo, and impaired podosome formation. Transcriptomic analysis revealed downregulation of genes involved in ribosome biogenesis. Moreover, ribosomal RNA accumulates in cell protrusions of migrating cells. We established that the craniofacial phenotype of the Sh3Pxd2bnee-/- mouse is governed by impaired cell migration and proliferation due to dysfunctional podosome formation, particularly in neural crest-derived tissues. Transcriptomic and molecular data suggest altered ribosome-related processes, although further investigation is needed to clarify the underlying mechanisms.
Nakakita B, Mizuta K, Katou Y
… +15 more, Tasaki H, Nakamura T, Yabuta Y, Iwatani C, Tsuchiya H, Kawamoto I, Tsukiyama T, Chen X, Bourque G, Otsuki J, Nakatsuka M, Horie A, Mandai M, Saitou M, Ohta H
Development
· 2026 Feb · PMID 41503675
·
Publisher ↗
Understanding the mechanisms for human ovarian folliculogenesis is fundamental to reproductive biology and medicine. Here, we investigated transcriptomic dynamics in individual oocytes and their associated granulosa cell...Understanding the mechanisms for human ovarian folliculogenesis is fundamental to reproductive biology and medicine. Here, we investigated transcriptomic dynamics in individual oocytes and their associated granulosa cells (GCs) during folliculogenesis in mice, monkeys and humans. Unlike mouse oocytes, which exhibited stage-specific, stepwise transcriptomic maturation, monkey and human oocytes showed minimal transcriptomic changes until the secondary follicle stage and could be broadly categorized as either immature or mature. In all three species, most highly variable genes during oocyte growth displayed monotonic up- or downregulation, with limited overlap in highly variable genes across species. GCs exhibited similarly species-specific transcriptomic trajectories. Correspondingly, intercellular communication pathways, including ligand-receptor signaling, gap junctions, and metabolic coupling between oocytes and GCs, demonstrated substantial species-specific differences. Nonetheless, X-chromosome dosage compensation and repression of evolutionarily young transposons were conserved across species. We established in vitro culture systems supporting preantral to antral follicle development in monkeys and humans, revealing relatively normal oocyte transcriptome maturation but aberrant GC profiles. By delineating interspecies differences in folliculogenesis, this study provides a framework for understanding human ovarian development and advancing its in vitro reconstruction.
Cwetsch AW, Ferreira S, Delberghe E
… +10 more, Gilabert-Juan J, Moreau MX, Saillour Y, García-Bolufer P, Calvo-Parra S, González-Martínez J, Massoukou D, Borello U, Causeret F, Pierani A
Development
· 2026 Jan · PMID 41493231
·
Full text
Brain development requires correct tissue patterning and production of appropriate cell types. Transcription factors play essential roles in these processes, regulating the expression of target genes responsible for the...Brain development requires correct tissue patterning and production of appropriate cell types. Transcription factors play essential roles in these processes, regulating the expression of target genes responsible for the specific features of neuronal subtypes. Cell adhesion molecules are key components of developmental processes that control cell sorting, migration, neurite outgrowth/guidance and synaptogenesis. To date, the link between transcription factors and cell adhesion molecules has been considered unidirectional. Here, we demonstrate that ectopic expression of Dbx1 leads to spatiotemporally restricted increased expression of Pcdh8 and cell aggregation, together with changes in neuronal identity. Surprisingly, ectopic Pcdh8 expression also induces Dbx1 expression, as well as a complete reorganisation of apico-basal polarity and dorso-ventral patterning via Notch signalling. Altogether, our work therefore points to cell adhesion molecules as unexpected, yet important, players in the regulation of cell identity and, in particular, Pcdh8 through its bidirectional interaction with the Dbx1 transcription factor.
Development
· 2026 Jan · PMID 41459783
·
Full text
Wdr5, a multifunctional scaffolding protein, with established roles in chromatin regulation and pluripotency, but its functions in early development remain poorly understood. Here, we show that Xenopus wdr5 is expressed...Wdr5, a multifunctional scaffolding protein, with established roles in chromatin regulation and pluripotency, but its functions in early development remain poorly understood. Here, we show that Xenopus wdr5 is expressed in blastula stem cells and enriched in neural crest cells. Depletion of wdr5 abolished neural crest gene expression in embryos and in reprogrammed explants while expanding neural plate border and neural plate domains. Gain-of-function experiments revealed striking dose-dependent effects: low Wdr5 enhanced neural crest formation, whereas high levels suppressed it, suggesting a requirement for precise stoichiometry with interacting partners. We identify Myc as an essential co-factor for Wdr5 in neural crest - Wdr5 and Myc physically interact and co-expression at defined ratios rescues neural crest formation. We further show that the Wdr5 WBM site is required for Myc-dependent activation of neural crest genes, whereas the WIN site regulates myc expression itself; both domains are necessary to rescue wdr5 depletion. These findings reveal that Wdr5 orchestrates neural crest development through multiple, domain-specific mechanisms, integrating stoichiometric control with partner-specific transcriptional regulation, and underscores the importance of precise co-factor ratios in cell fate decisions.
Development
· 2025 Dec · PMID 41416747
·
Publisher ↗
The striped gene expression pattern of the pair-rule genes along the Drosophila embryo requires tight coordination by regulatory elements. In a recent study, Fischer et al. reveal that regulatory elements with overlappin...The striped gene expression pattern of the pair-rule genes along the Drosophila embryo requires tight coordination by regulatory elements. In a recent study, Fischer et al. reveal that regulatory elements with overlapping functions show compensatory mechanisms in driving the expression of two pair-rule genes: eve and ftz. To find out more, we spoke to first author Matthew Fischer and corresponding author Leslie Pick, Professor at the University of Maryland, USA.
Qian Q, Nagai H, Sanaki Y
… +4 more, Hayashi M, Kimura K, Nakajima YI, Niwa R
Development
· 2026 Jan · PMID 41392708
·
Publisher ↗
Cellular plasticity, the ability of a differentiated cell to adopt another phenotypic identity, is restricted under basal conditions, but can be elicited upon damage. However, the molecular mechanism enabling such plasti...Cellular plasticity, the ability of a differentiated cell to adopt another phenotypic identity, is restricted under basal conditions, but can be elicited upon damage. However, the molecular mechanism enabling such plasticity remains largely unexplored. Here, we report damage-induced cellular plasticity of secretory enteroendocrine cells (EEs) in the adult Drosophila midgut. Ionizing radiation induces EE fate conversion and activates stress-responsive programs in EE lineages, accompanied by the induction of the stress-inducible transcription factor Xrp1 and the cytokine gene upd3. Xrp1 and upd3 are both necessary for radiation-induced EE plasticity. Under basal conditions, EE-specific Xrp1 overexpression triggers ectopic expression of progenitor-specific genes, which is necessary for Xrp1 to drive EE plasticity. Our work identifies Xrp1 as a crucial regulator that coordinates damage-induced signaling and transcriptional reprogramming, enabling the reactivation of cellular plasticity in differentiated cells.
Demurtas M, Barnada SM, van Domselaar E
… +3 more, Mitchell ZH, Deelen L, Trizzino M
Development
· 2025 Dec · PMID 41312722
·
Full text
Neural crest induction begins early during neural plate formation, requiring precise transcriptional control to activate lineage-specific enhancers. Here, we demonstrate that SALL4, a transcription factor associated with...Neural crest induction begins early during neural plate formation, requiring precise transcriptional control to activate lineage-specific enhancers. Here, we demonstrate that SALL4, a transcription factor associated with syndromes featuring craniofacial anomalies, plays a crucial role in early cranial neural crest (CNCC) specification. Using SALL4-het-KO human iPSCs to model clinical haploinsufficiency, we show that SALL4 directly recruits BAF to CNCC-lineage specific enhancers at the neuroectodermal stage, specifically when neural crest gene expression is induced at the neural plate border. Without functional SALL4, BAF is not loaded at chromatin, leaving CNCC enhancers inaccessible. Consequently, the cells cannot undergo proper CNCC induction and specification due to persistent enhancer repression, despite normal neuroectodermal and neural plate progression. Moreover, by performing SALL4 isoform-specific depletion, we demonstrate that SALL4A is the isoform essential for CNCC induction and specification, and that SALL4B cannot compensate for SALL4A loss in this developmental process. In summary, our findings reveal SALL4 as essential regulator of BAF-dependent enhancer activation during early stages of neural crest development, providing molecular insights into SALL4-associated craniofacial anomalies.
Fischer MD, Au K, Lê M
… +2 more, Graham P, Pick L
Development
· 2025 Dec · PMID 41293990
·
Full text
The striped expression of pair-rule genes in Drosophila embryos is a paradigm for understanding transcriptional control of development. Pair-rule striped expression is regulated by two types of cis-regulatory elements: s...The striped expression of pair-rule genes in Drosophila embryos is a paradigm for understanding transcriptional control of development. Pair-rule striped expression is regulated by two types of cis-regulatory elements: stripe-specific elements respond to non-periodic cues in different regions of the embryo to establish individual stripes while 7-stripe elements simultaneously regulate all stripes, responding to pair-rule genes expressed in stripes. Here, we assess roles of stripe-specific versus 7-stripe elements for the pair-rule gene ftz. We show that loss of a ftz stripe 2 element is compensated by 7-stripe elements, even though they respond to different spatiotemporal cues. We next investigate whether similar rules apply to the classic eve stripe2 element. Animals homozygous for a genomic deletion of eve stripe2 are viable and fertile; stripe 2 expression is perturbed early but re-establishes sufficiently to regulate downstream target genes. However, temperature or genetic stress decrease viability of ftz and eve stripe 2 deletion mutants. Thus, these stripe-specific elements contribute to robustness but are not absolutely required for segment formation. Two separate routes to establishing stripes, stripe-specific and 7-stripe elements, buffer each other, adding complexity to embryonic patterning.
Katbe A, Hanna R, Flamier A
… +6 more, Serhani D, Hamam R, Barabino A, Tavares E, Héon É, Bernier G
Development
· 2026 Jan · PMID 41293951
·
Publisher ↗
Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) resets the aging clock. However, primed iPSCs can retain cell-of-origin epigenomic marks, especially those linked to heterochromatin. Here,...Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) resets the aging clock. However, primed iPSCs can retain cell-of-origin epigenomic marks, especially those linked to heterochromatin. Here, we show that iPSCs produced from fibroblasts of late-onset sporadic Alzheimer's disease (AD) cases retain epigenomic alterations that correlate with developmental anomalies and neurodegeneration. Compared to controls, AD iPSCs show reduced BMI1 expression and H3K9me3 levels and an altered DNA methylome. Gene Ontology analysis of differentially methylated DNA regions reveals terms linked to cell-cell adhesion and synapses, with MEF2C-binding sites being the most enriched at differentially methylated DNA regions. Upon noggin exposure, AD iPSCs show less-efficient neural induction and forebrain specification, together with elevated WNT signaling. Mature AD neurons present a mixed cell lineage identity phenotype and reduced MEF2C expression. AD glial cells express neuronal, cell proliferation, and stem cell-related genes. Despite these anomalies, AD iPSCs generate cortical neurons in normal proportion and readily form cerebral organoids showing AD-related pathologies. These findings implicate reprogramming-resistant epigenomic alterations or genetic variants working in trans on the epigenome in AD pathophysiology.
Christensen JB, Donovan APA, Moradi M
… +7 more, Vanacore G, Helmy M, Reid AJ, Lee JTH, Bayraktar OA, Brand AH, Bayin NS
Development
· 2025 Dec · PMID 41287940
·
Full text
Understanding the molecular mechanisms driving lineage decisions and differentiation during development is challenging in complex systems with a diverse progenitor pool, such as the mammalian cerebellum. Importantly, how...Understanding the molecular mechanisms driving lineage decisions and differentiation during development is challenging in complex systems with a diverse progenitor pool, such as the mammalian cerebellum. Importantly, how different transcription factors cooperate to generate neural diversity and the gene regulatory mechanisms that drive neuron production, especially during the late stages of cerebellum development, are poorly understood. We used single cell RNA-sequencing (scRNA-seq) to investigate the developmental trajectories of nestin-expressing progenitors (NEPs) in the neonatal mouse cerebellum. We identified FOXO1 as a key regulator of NEP-to-inhibitory neuron differentiation, acting directly downstream of ASCL1. Genome occupancy and functional experiments using primary NEP cultures showed that both ASCL1 and FOXO1 regulate neurogenesis genes during differentiation while independently regulating proliferation and survival, respectively. Furthermore, we demonstrated that WNT signalling promotes the transition from an ASCL1+ to a FOXO1+ cellular state. Finally, the role of WNT signalling in promoting neuron production via FOXO1 is conserved in primary human NEP cultures. By resolving how cerebellar inhibitory neurons differentiate, our findings could have implications for cerebellar disorders such as spinocerebellar ataxia, where these cells are overproduced.
Balayo T, Lunn S, Pascual-Mas P
… +9 more, Fiuza UM, Vasudevan A, Frenster JD, Josende García JB, Galloon HY, Peirats RF, Arias AM, Dias A, Turner DA
Development
· 2025 Nov · PMID 41287934
·
Full text
Gastruloids are 3D aggregates of pluripotent stem cells grown in suspension culture that mimic many aspects of gastrulation and early axial elongation. The N2B27 basal medium in which mouse gastruloids are cultured can e...Gastruloids are 3D aggregates of pluripotent stem cells grown in suspension culture that mimic many aspects of gastrulation and early axial elongation. The N2B27 basal medium in which mouse gastruloids are cultured can either be home-made (HM-N2B27) with materials of known origin, or commercially sourced (NDiff227), where the exact formulation is unknown. In this study, we examined whether these formulations resulted in significant differences in gastruloid development. Our results reveal that while both media enable standard gastruloid elongation, HM-N2B27 gastruloids initiate the elongation process earlier, have a higher number of cells and an increased anterior domain. Despite the maintenance of overall gene expression patterns, RNAseq analysis indicated differences in cell fate specification, with HM-N2B27 gastruloids exhibiting higher expression of spinal cord-related genes, while NDiff227 favours mesodermal differentiation. Furthermore, differential gene enrichment analysis suggests that changes in key signalling pathways underlie the differences between HM-N2B27 and NDiff227 gastruloids. These findings highlight the importance of basal media composition for gastruloid development, underscoring the need for careful media selection during in vitro engineering of stem cell-based embryo models.
Matsubara K, Hirota M, Kajiwara K
… +4 more, Senga H, Matsui S, Marutani M, Seki Y
Development
· 2025 Dec · PMID 41267649
·
Publisher ↗
The network of transcription factors is dynamically reorganized during the transition from naïve- to formative-pluripotency. In mice, Prdm14 is expressed in naïve pluripotent cells but rapidly downregulated upon exit fro...The network of transcription factors is dynamically reorganized during the transition from naïve- to formative-pluripotency. In mice, Prdm14 is expressed in naïve pluripotent cells but rapidly downregulated upon exit from the naïve state. In contrast, PRDM14 expression persists throughout pluripotency transitions in non-rodent mammals, including pigs and humans. Here, we investigate the molecular mechanisms underlying the rodent-specific expression of Prdm14. Using CRISPR/Cas9-mediated deletions, we demonstrated that POU5F1 and TFCP2L1 recognition sequences within Muroidea-specific cis-regulatory elements located downstream of Prdm14 are essential for its transcriptional upregulation in naïve embryonic stem cells. Loss of these enhancers attenuates the upregulation of Prdm14, leading to reduced Pramel7 induction and impaired degradation of UHRF1, which consequently diminished global DNA demethylation under 2iL conditions. Moreover, deletion of PRDM14-binding motifs in Muroidea-specific enhancers disrupts its negative feedback loop, resulting in a delayed transition from the naïve to formative pluripotent state. Our findings reveal that rodent-specific enhancer insertions endow Prdm14 with a dynamic regulatory architecture, enabling both activation and repression that collectively ensure the timely exit from naïve pluripotency during early embryogenesis.
Logan CY, Lim X, Fish MP
… +3 more, Mizutani M, Swain B, Nusse R
Development
· 2025 Dec · PMID 41263055
·
Full text
The capacity to detect and respond to injury is crucial for the recovery and long-term survival of many organisms. Wnts are commonly induced by tissue damage but how they become activated transcriptionally is not well un...The capacity to detect and respond to injury is crucial for the recovery and long-term survival of many organisms. Wnts are commonly induced by tissue damage but how they become activated transcriptionally is not well understood. Here, we report that mouse Wnt1 and Wnt10b are induced following injury in both lung and muscle. These Wnts occupy the same chromosome and are transcribed in opposite directions with 12 kb between them. We identified a highly conserved cis-acting regulatory region (enhancer) residing between Wnt1 and Wnt10b that, when fused to a lacZ reporter, is activated post-injury. This enhancer harbors putative AP-1-binding sites that are required for reporter activity, a feature observed in other injury-responsive enhancers. Injured muscles in mice carrying a germline deletion of the enhancer region display reduced Wnt1 and Wnt10b expression and show elevated intramuscular adipogenesis, which can be a hallmark of impaired muscle regeneration or tissue maintenance. Enhancer redundancy is common in development, but our in vivo analysis shows that loss of a single injury-responsive regulatory region in adult tissues can produce a detectable phenotype.
Development
· 2025 Dec · PMID 41243651
·
Full text
Cell fusion is a fundamental process in the development of many multicellular organisms, but its precise role in gene regulation and differentiation remains largely unknown. The Caenorhabditis elegans epidermis, which co...Cell fusion is a fundamental process in the development of many multicellular organisms, but its precise role in gene regulation and differentiation remains largely unknown. The Caenorhabditis elegans epidermis, which comprises multiple syncytial cells in the adult, represents a powerful model for studying cell fusion in the context of animal development. The largest of these epidermal syncytia, hyp7, integrates 139 individual nuclei through processive cell fusion mediated by the fusogenic protein EFF-1. To explore the role of cell fusion in developmental progression and associated gene expression changes, we conducted transcriptomic analyses of eff-1 fusion-defective C. elegans mutants. Our RNA-seq findings showed widespread transcriptomic changes including the enrichment of epidermal genes and molecular pathways involved in epidermal function during development. Single-molecule fluorescence in situ hybridization further validated the observed altered expression of mRNA transcripts. Moreover, bioinformatic analysis suggests that fusion may play a key role in promoting developmental progression within the epidermis. Our results underscore the significance of cell-cell fusion in shaping transcriptional programs during development.