eLife: latest articles by subject

Bidirectional redistribution of actomyosin drives epithelial invagination in ascidian siphon tube morphogenesis

libome@tsinghua.edu.cn (Bo Dong) — Thu, 01 Oct 2026 00:00:00 +0000

How epithelia perform a spatiotemporal heterogeneous force-generating program to drive a sequential tissue morphogenesis remains unclear, particularly the underlying precise mechanical mechanisms. This study investigated dynamic actomyosin reorganization between apical and lateral membrane cortex regions during two sequentially invaginated stages of atrial siphon tube morphogenesis in the ascidian Ciona. At the initial invagination stage, the originally lateral-located actomyosin redistributed to the apical domains, while that actomyosin redistributed back to lateral domains at the accelerated invagination stage. Using genetic mutants to modulate myosin activities, the initial invagination was strengthened or abolished, indicating invagination is apical constriction-dependent. Optogenetic inhibition of myosin activities in lateral domains after initial invagination stage blocked the further processes, suggesting lateral constriction of actomyosin is required for the accelerated invagination. Vertex model simulations uncovered a coupled mechanism underlying epithelial invagination driven by apicobasal tension imbalance and lateral contraction. We thus propose an actomyosin redistribution mechanical model: lateral actomyosin first redistributes apically to drive apical constriction and shape the initial invagination, then apical actomyosin redistributes laterally to promote lateral contractility and accelerate invagination. Our findings reveal a bidirectional reorganization of the actomyosin network as a central mechanism driving epithelial invagination, providing insights on epithelial invagination and organ morphogenesis during development.

Genome-wide discovery of cis-regulatory elements in a large genome

michalis.averof@ens-lyon.fr (Çağrı Çevrim) — Thu, 01 Oct 2026 00:00:00 +0000

Identifying cis-regulatory elements typically relies on trial and error to test the activity of DNA fragments using reporter constructs. This approach is particularly challenging in large eukaryotic genomes, where cis-regulatory elements can be dispersed over long distances, separated by large stretches of non-functional DNA. Here, we generate two types of resources that can be used to narrow the search for such elements in the 3.6 Gbp genome of Parhyale hawaiensis. First, we use bulk ATAC-seq to uncover genome-wide patterns of chromatin accessibility in Parhyale embryonic and adult tissues, and single-nucleus ATAC-seq to identify regions of open chromatin in diverse cell types. Second, by sequencing the genomes of three congeneric species – P. darvishi, P. aquilina, and P. plumicornis – we identify islands of sequence conservation across the genome, likely corresponding to functionally constrained DNA. We find that low-coverage (10–15×) short-read genome sequencing, without genome assembly, is sufficient to provide reliable maps of sequence conservation. This approach cuts the cost and labour required to generate these maps, making the identification of cis-regulatory elements more widely accessible. We demonstrate the utility of these resources by identifying cis-regulatory elements that drive robust expression of fluorescent reporters ubiquitously and in specific cell types.

Zinc is a key regulator of the sperm-specific K⁺ channel (Slo3) function

kawai.takafumi.ra@ehime-u.ac.jp (Haruhiko Miyata) — Wed, 30 Sep 2026 00:00:00 +0000

The voltage- and pH-gated Slo3 potassium channel is exclusively expressed in mammalian spermatozoa. Its sensitivity to both voltage and alkalization plays a crucial role in sperm fertility, which is tightly coupled to the capacitation process. Here, we show that sperm-enriched divalent cation Zn²⁺ undergoes dynamic alteration in spermatozoa during capacitation. We also found that intracellular Zn²⁺ regulates alkalinization-induced hyperpolarization in mouse spermatozoa, which is mediated by the Slo3 channel. Further examination of zinc regulation in mouse Slo3 (mSlo3) revealed that, in the Xenopus oocyte expression system, intracellular zinc directly inhibits mouse Slo3 currents in a dose-dependent manner at micromolar concentrations, with exceptionally slow dissociation. By combining MD simulations and electrophysiology, we also identified amino acid residues contributing to the Zn²⁺ slow dissociation from Slo3 channels. Our studies uncover the importance of intracellular zinc dynamics and its regulatory role in ion channels during sperm capacitation.

Single-cell spatial mapping reveals reproducible cell type organization and spatially dependent gene expression in gastruloids

arjunrajlab@gmail.com (Arjun Raj) — Tue, 29 Sep 2026 00:00:00 +0000

Gastruloids are stem-cell-based models that recapitulate key aspects of mammalian gastrulation, including the formation of an anterior-posterior axis. However, we do not have detailed spatial information about gene expression and cell type organization, particularly at the level of individual gastruloids. Here, we report a spatially resolved, single-cell molecular catalog of the transcriptomes of 26 individual gastruloids. We found that cell type composition and tissue-scale spatial organization were largely consistent across gastruloids, but meso-scale patterning of specific cell types varied between samples. Posterior cell types formed distinct, organized clusters, while anterior cell types were more disorganized. To distinguish progressive differentiation from cell type differences, we developed the L-score, a parameter-free quantification of mutually exclusive gene expression. This analysis revealed spatial organization without explicit encoding, recapitulated known cell type relationships, and identified novel gene expression states and spatial subclusters within cell types. We confirmed that in gastruloids, neuromesodermal precursor differentiation occurred through a continuous, spatially coordinated process. We also showed that endothelial precursors exhibited unique spatial organization and had distinct gene expression profiles dependent on their association with anterior somitic or posterior endodermal tissues. This work enables the rigorous use of gastruloids as models for studying the molecular mechanisms underlying mammalian development and tissue organization and introduces new computational tools for analyzing spatially resolved single-cell datasets.

Cellular basis of accelerated whole-tooth regeneration

todd.streelman@biology.gatech.edu (Anoushka Satoskar) — Thu, 24 Sep 2026 00:00:00 +0000

Teeth are ectodermal organs that have, throughout their long evolutionary history, retained the capacity for full regeneration and replacement, even in adult stages. Yet, because most mammals (e.g., humans, mice) lack lifelong dental replacement, we do not fully understand its tempo and mode, and we do not have a clear picture of the cell populations and signals that contribute to the process. Here, we used cichlid fishes from Lake Malawi, species that differ in tooth formula (tooth shape and number) but share one-for-one tooth replacement, to (i) explore the tempo of dental replacement after plucking and then (ii) identify the cell populations, gene expression signatures, and interactions between cell populations that change in this plucking paradigm. We observed that cichlid species with divergent dentitions accelerated tooth replacement >3× on the plucked half of the jaw. Then, we used single-nucleus RNA-seq to profile cellular and molecular changes across the first week of post-plucking tooth replacement. This approach allowed us to infer cellular trajectories in dental epithelium and mesenchyme that underlie tooth regeneration. We identified distinct gene expression profiles and cellular interactions across four time points of accelerated tooth replacement, with divergent involvement of epithelial, mesenchymal, and immune cell types. Differential signaling of Collagen, BMP, MMP, Semaphorin, and Slit-Robo pathways was evident after plucking and highlights temporally sequenced roles of immune response, odontogenesis, vascularization, and nerve pathfinding as teeth are constructed anew. Overall, this study provides insight into the trajectory of cellular interactions accompanying whole-tooth replacement and offers a comparative foundation for understanding dental regeneration in vertebrates.

PRMT1-SFPQ regulates intron retention to control matrix gene expression during craniofacial development

wpeng@gwu.edu (Amy E Merrill) — Tue, 22 Sep 2026 00:00:00 +0000

Spliceosomopathies, which are a group of disorders caused by defects in the splicing machinery, frequently affect the craniofacial skeleton and limb, but the molecular mechanism underlying this tissue-specific sensitivity remains unclear. Splicing factors and small nuclear ribonucleoproteins (snRNPs) are core components of splicing machinery, and splicing factors are further controlled by post-translational modifications, among which arginine methylation is one of the most prevalent. We determined the splicing mechanisms in the cranial neural crest cells (CNCCs), a multipotent developmental population that gives rise to the majority of the craniofacial skeleton, and focused on an upstream regulator of splicing proteins, protein arginine methyltransferase 1 (PRMT1). PRMT1 is the highest expressing arginine methyltransferase in CNCCs, and its role in craniofacial development is evident from our earlier investigation, where CNCC-specific Prmt1 deletion caused cleft palate and mandibular hypoplasia. PRMT1 catalyzes arginine methylation of splicing factors to modify protein localization, expression, and activity. In the present study, we uncover roles of PRMT1 in the regulation of intron retention, a type of alternative splicing where introns are retained in the mature mRNA. CNCCs from the mandibular primordium of Prmt1-deficient embryos demonstrated an increase in the percentage of intron-retaining mRNA of matrix genes, which triggered nonsense-mediated decay (NMD), causing a reduction in matrix mRNA abundance. We further identified SFPQ as a substrate of PRMT1 that depends on PRMT1 for arginine methylation and protein expression in the developing craniofacial structures. Depletion of SFPQ in CNCCs phenocopied PRMT1 deletion whereby matrix, Wnt signaling components, and neuronal gene transcripts contained higher IR and exhibited lower expression. We further recognized gene length as a common feature among SFPQ-regulated genes in CNCCs. Altogether, these findings demonstrate that the PRMT1-SFPQ pathway modulates matrix gene expression via IR-triggered NMD in CNCCs during craniofacial development.

MATR3 is essential for oocyte growth and maturation quality through a dual molecular mechanism

hr7424@126.com (Bingying Liu) — Mon, 21 Sep 2026 00:00:00 +0000

The molecular mechanisms governing mRNA accumulation during oocyte growth, essential for developmental competence, remain poorly understood. This study investigates the role of Matrin-3 (MATR3), a highly expressed RNA-binding protein in growing oocytes (GOs), using oocyte-specific knockout mouse models and human oocyte maturation arrest (OMA) samples. The results showed that MATR3 was more abundant in GOs than fully grown oocytes (FGOs), highly expressed in the nucleus of non-surrounded nucleolus (NSN) oocytes, and exited the nucleus during the NSN-to-surrounded nucleolus (SN) transition. In OMA patients, MATR3 nuclear localization was missed, with smaller oocytes than FGOs. Further, Matr3 deletion in mouse GOs caused restricted oocyte growth, global transcription disorders, follicle development failure, blocked GO-granulosa cell communication (via reduced Gdf9 and Rdx expression), and infertility. Mechanistically, MATR3 regulated transcription by recruiting H3K9me2-demethylating lysine-specific demethylase 3B or binding target gene promoters, like Rdx. These findings reveal a critical role of MATR3 in orchestrating transcription and paracrine signaling during oogenesis and suggest its potential as a diagnostic and therapeutic target for OMA.

In vitro sexual dimorphism establishment in schistosomes

Matt.Berriman@glasgow.ac.uk (Benjamin J Hulme) — Thu, 10 Sep 2026 00:00:00 +0000

Schistosomes are parasitic flatworms that cause Schistosomiasis, a major neglected tropical disease that affects more than 250 million people worldwide. With two distinct sexes, a heterogametic female (ZW) and a homogametic male (ZZ), schistosomes are an exception among flatworms, which are largely hermaphroditic. Sexual dimorphism in schistosomes only becomes apparent by adulthood within the mammalian host. However, the cellular and molecular mechanisms underlying the sexual differentiation of are poorly understood, partly due to intrinsic challenges in assessing parasite development in vivo. Therefore, robust and reproducible approaches for maintaining and developing parasites in vitro are needed to overcome these difficulties. To date, few studies have focused on protocols that allow cultured parasites to reach sexual dimorphic stages, and none have been reproduced, limiting the ability to understand the sexual biology of this major human parasite. Here, we refine a protocol for long-term culture of newly transformed cercariae that developed in vitro into sexually dimorphic forms. We assessed the effect of adding two different sera, foetal bovine serium (FBS) and human serum (HS), to culture medium supplemented with red blood cells. In contrast to FBS-culture parasites, those grown in HS digested red blood cells, a crucial step for long term parasite development. Furthermore, sexual dimorphism was clearly established in the HS-cultured parasites, albeit delayed, in contrast to most FBS-cultured parasites that did not progress beyond an early liver stage. Moreover, in EdU-pulse experiments, cells within HS-cultured parasites continuously proliferated, but markedly fewer proliferated in FBS-culture. By enabling reproducible parasite develoment in vitro, this protocol creates new opportunities for dissecting mechanisms that underly sexual dimorphim, as well as for screening in vitro for new interventions across the life cycle of these major human parasites.

Primordial cardiomyocytes orchestrate myocardial morphogenesis and vascularization but are dispensable for regeneration

jisheng_sun@fudan.edu.cn (Jinhu Wang) — Tue, 08 Sep 2026 00:00:00 +0000

The vertebrate heart is composed of heterogeneous cardiomyocyte (CM) populations; however, the roles of distinct CM subpopulations in heart development and repair remain poorly defined. Here, using single-cell RNA sequencing analysis of adult zebrafish heart, we identified a unique CM subpopulation marked by the expression of phlda2, which is associated with anaerobic metabolism and different from mature CMs, which are enriched for oxidative phosphorylation genes. We demonstrated that phlda2⁺ cells constituted a primordial CM compartment localized between compact and trabecular muscles. Genetic ablation of phlda2⁺ CMs during development severely disrupted heart morphogenesis, leading to defective myocardial trabeculation and compaction, and impaired coronary vascularization. Surprisingly, despite their essential roles in development, the depletion of phlda2⁺ CMs didn’t impair myocardial restoration and revascularization following ventricular resection. We found that this was probably due to the limited regenerative capacity of the primordial CMs themselves, as they failed to regenerate after either surgical amputation or genetic ablation. Our findings identify primordial CMs as an organizer for heart morphogenesis but not essential for regeneration, revealing a fundamental difference between developmental and regenerative programs in the vertebrate heart.

Trpv4 links environmental temperature to testicular differentiation in hermaphroditic ricefield eel

sunyh@ihb.ac.cn (Tingting Luo) — Mon, 07 Sep 2026 00:00:00 +0000

The ricefield eel (Monopterus albus), an economically important aquaculture species in China, is a freshwater teleost fish that exhibits protogynous hermaphroditism. Although progress has been made in understanding the sex determination and differentiation of this species, the underlying mechanisms remain unclear. Here, we show that warm temperature promotes gonadal transformation by up-regulating testicular differentiation genes, such as dmrt1/sox9a in ovaries. Trpv4, a Ca²⁺-permeable cation channel expressed in gonadal somatic cells, is highly sensitive to ambient temperature and links environmental temperature to testicular differentiation in ricefield eel. In female fish reared at cool temperature, injection of Trpv4 agonist into the ovaries leads to a significant upregulation of male pathway genes and in female fish exposed to warm temperature, Trpv4 inhibition or trpv4 siRNA knockdown suppresses warm temperature-induced male gene expression. pStat3 signaling is downstream of Trpv4 and transduces Trpv4-controlled calcium signaling into the sex determination cascades. Inhibition of pStat3 activity prevents the up-regulation of testicular differentiation genes by warm temperature treatment and ovarian injection of Trpv4 agonist, whereas activation of pStat3 is sufficient to induce the expression of male genes in the presence of Trpv4 antagonist. pStat3 binds and activates jmjd3/kdm6b, an activator of the dmrt1 gene. Consistently, ovarian injection of Kdm6b inhibitor blocks the up-regulation of testicular differentiation genes by warm temperature exposure. We propose that environmental factors, such as temperature, promote gonadal transformation of ricefield eel by inducing the expression of male pathway genes in ovaries via the Trpv4-pStat3-Kdm6b-dmrt1 axis. Our results provide new insights into the molecular mechanism underlying natural sex change of ricefield eel, which will be useful for sex control in aquaculture.

Complementary vertebrate Wac models exhibit phenotypes relevant to DeSanto-Shinawi Syndrome

zebrakim@cnu.ac.kr (Alex S Nord) — Thu, 03 Sep 2026 00:00:00 +0000

Monogenic syndromes are associated with neurodevelopmental changes that result in cognitive impairments and neurobehavioral phenotypes, including autism and seizures. Limited studies and resources are available to make meaningful headway into the underlying molecular mechanisms that result in these symptoms. One such example is DeSanto-Shinawi Syndrome (DESSH), a rare disorder caused by pathogenic variants in the WAC gene. Individuals with DESSH syndrome exhibit a recognizable craniofacial gestalt, developmental delay/intellectual disability, neurobehavioral symptoms that include autism, ADHD, behavioral difficulties, and seizures. However, no thorough studies from a vertebrate model exist to understand how these changes occur. To overcome this, we developed both murine and zebrafish Wac/wac deletion mutants and studied whether their phenotypes recapitulate those described in individuals with DESSH syndrome. We first show that the two Wac models exhibit craniofacial and behavioral changes, reminiscent of abnormalities found in DESSH syndrome. In addition, each model revealed impacts on GABAergic neurons and further studies showed that the mouse mutants are susceptible to seizures, changes in brain volumes that are different between sexes and relevant behaviors. Finally, we uncovered transcriptional impacts of Wac loss-of-function in mice that will pave the way for future molecular studies into DESSH. These studies present two new vertebrate models that begin to uncover biological underpinnings of DESSH syndrome and elucidate the biology of Wac.

Multiple molecular pathways to longevity with opposing gene expression programs defining distinct aging strategies in Caenorhabditis elegans

jeremy.vanraamsdonk@mcgill.ca (Aura A Tamez Gonzalez) — Thu, 20 Aug 2026 00:00:00 +0000

While aging is the greatest risk factor for the development of neurodegenerative disease, the role of aging in these diseases is poorly understood. Our previous work has shown that targeting aging pathways can be neuroprotective in animal models of neurodegenerative disease. Based on these findings, we believe that by gaining insight into the aging process that knowledge can be applied to identify novel therapeutic targets for neurodegenerative disease. To advance our understanding of aging, we used a genomics approach to identify genes regulated by multiple lifespan-extending pathways. We performed RNA sequencing on nine long-lived Caenorhabditis elegans mutants representing seven longevity pathways: insulin/IGF-1 signaling, dietary restriction, germline deficiency, impaired chemosensation, reduced translation, elevated mitochondrial ROS, and mild mitochondrial impairment. We found that most pairs of long-lived mutants exhibited a significant overlap in differentially expressed genes. Comparing gene expression across the entire panel of long-lived mutants revealed three distinct longevity groups that could be clearly distinguished by gene expression. Interestingly, two of these groups showed modulation of specific genetic pathways in opposite directions, suggesting that there are multiple alternative strategies to achieving long life. Filtering for genes similarly modulated in at least six mutants identified 196 upregulated and 62 downregulated aging genes. Upregulated genes were enriched in immunity, defense, and metabolism, while many downregulated genes impacted translation and gene expression. To assess the ability of these genes to enhance longevity individually, we knocked down the commonly upregulated genes in long-lived mutants and evaluated the resulting effect on lifespan. Using this approach, we identified several genes that affect lifespan individually. Upregulation of at least some of these genes was sufficient to enhance stress resistance and extend lifespan in wild-type worms. Overall, the shared longevity genes identified in this work offer potential targets to promote healthy aging and decrease age-onset disease.

Latent gene network expression underlies partial re-evolution of a polyphenic trait in the worker caste of ants

abouheif@zju.edu.cn (Angelly Vasquez-Correa) — Tue, 18 Aug 2026 00:00:00 +0000

Polyphenisms–where alternative phenotypes develop from a single genome in response to environmental cues–are not only widespread in nature, but also occur at multiple levels of biological organization, from cells to individuals to societies. Polyphenism is thought to promote phenotypic diversification through the gain, loss, and re-evolution of alternative phenotypes. After the origin of a polyphenism, one of the alternative phenotypes often retains the developmental capacity to produce the ancestral trait, thereby permitting the other to evolve rapidly. Yet, little is known about the developmental processes underlying the re-evolution of polyphenic traits, and how they may produce phenotypic diversification. Here, we address this question by focusing on the caste polyphenism in ant societies, which produces a winged queen caste and a wingless worker caste in a single colony in response to environmental cues. We show, in a hyperdiverse group of ants, that a caste-specific trait called the ocelli (three simple eyes on the dorsal head) is always present across queen castes but was lost and partially re-evolved multiple times, giving rise to novel patterns (one ocelli) in the worker castes. Surprisingly, we discovered that a hidden (latent) expression of the ocelli gene regulatory network in worker castes that lost ocelli underlies the partial re-evolution of ocelli in this group. We therefore propose that latent developmental potentials may generally persist across polyphenic systems, including ant castes, and may facilitate the partial re-evolution of novel phenotypic patterns.

Nucleation-dependent propagation of Polycomb modifications emerges during the Drosophila maternal to zygotic transition

shelby.blythe@northwestern.edu (Corinne Croslyn) — Thu, 13 Aug 2026 00:00:00 +0000

During zygotic genome activation in Drosophila, broad domains of Polycomb-modified chromatin are rapidly established across the genome. Here, we investigate the spatial and temporal dynamics by which Polycomb group (PcG) histone modifications, H3K27me3 and H2Aub, emerge during early embryogenesis. Using ChIP-seq and live imaging of CRISPR-engineered GFP-tagged PcG components, we show that PRC2-dependent H3K27me3 accumulates adjacent to a subset of E(z)-bound prospective Polycomb response elements (PREs) beginning in nuclear cycle 14 (NC14), with patterns indicative of nucleation followed by spreading. Surprisingly, PRE-binding factors Pho, Combgap, and GAGA-factor are excluded from interphase nuclei prior to NC10, despite nuclear localization of E(z) throughout early interphases. Loss-of-function studies further demonstrate that GAGA-factor is largely dispensable for PcG domain establishment, whereas the pioneer factor Zelda is required for proper deposition of H3K27me3 and H2Aub at a subset of Polycomb domains. The role of Zelda at Polycomb domains is context-dependent; a subset of targets requires Zelda not for E(z) recruitment, but instead to license an E(z)-loaded PRE to deposit H3K27me3. Our findings support a model where licensing of PcG domains is an initial step in the regulatory processes governing Polycomb-regulated developmental genes.

Following your heart as it takes shape

nicole.dubois@mssm.edu (Alexandra Trouilloud) — Fri, 31 Jul 2026 00:00:00 +0000

A novel computational pipeline reveals patterns of tissue movement and growth in early heart formation and advances virtual modeling of development.

Quantitative computerized analysis demonstrates strongly compartmentalized tissue deformation patterns underlying mammalian heart tube formation

jorgendm@ujaen.es (Jorge N Domínguez) — Tue, 21 Jul 2026 00:00:00 +0000

The quantitative analysis of tissue deformation at cellular resolution remains an important challenge in mammalian organogenesis. Here, we developed a new computational workflow to extract regional and temporal patterns of tissue deformation, and applied it to a collection of live microscopy datasets from mouse cardiogenesis. We devised a method to track tissue deformation directly from time-lapse raw images and experimentally validated the method by comparison with actual cell tracks. We then used a machine-learning approach to temporally and spatially align different specimens and reconstruct a single statistical model of tissue motion, deducing maps of strain, anisotropy, and tissue growth. We also implemented a virtual fate mapping tool that allows tracking any initial position in the cardiac primordium onto the linear heart tube (HT). Our study reveals predominant local cellular coherence during the deformation of the cardiac tissue, whereas strong compartmentalization of tissue deformation patterns transforms the bilateral cardiac primordium into a 3D longitudinal HT. At the future outer curvature of the primitive tube, the ventricular chamber forms by expansion of the tissue in a hemi-barrel shape with two harnessing belts: one that constrains tissue expansion at the arterial pole and one that constrains the expansion at the venous pole. Our study provides a new approach to understanding heart morphogenesis and proposes a new model of primitive HT formation.

Single-cell characterization of anterior segment development in the mouse reveals the cell types, pathways, and signals driving formation of the trabecular meshwork and Schlemm’s canal

rb3132@cumc.columbia.edu (Aakriti Bhandari) — Tue, 21 Jul 2026 00:00:00 +0000

Morphogenesis of the anterior segment (AS) is crucial for healthy ocular physiology and vision, but is only partially understood. The Schlemm’s canal (SC) and trabecular meshwork (TM) are essential drainage tissues within the AS, and their proper development and function are critical for maintaining normal intraocular pressure; abnormalities in either tissue can result in elevated pressure and glaucoma. Here, we use single-cell transcriptomic profiling to provide high-resolution molecular detail of mouse AS development with a particular focus on SC and TM. We report transcriptomes for ~130,000 single cells at key developmental stages from postnatal day 2 (P2) to P60. We provide the first annotation of cell types across these developmental stages and crucial information about dynamic changes in pathways/gene expression. Further, we trace developmental trajectories for TM cell and SC endothelial cell (SEC) subtypes and determine genes and signaling networks driving their specific cell fates. We demonstrate dynamic changes in signaling interactions between SC and the TM cells during their synchronized development. Collectively, our data lay a deep molecular foundation for AS development that will direct understanding of normal ocular physiology, glaucoma, and other AS conditions.

Flexible and high-throughput simultaneous profiling of gene expression and chromatin accessibility in single cells

volker_soltys@eva.mpg.de (Dingwen Su) — Mon, 20 Jul 2026 00:00:00 +0000

Gene regulation underpins development and is an intricate biological process involving transcription, typically at promoters within accessible chromatin. To understand cell-type-specific regulatory networks, the ability to capture both transcription and chromatin accessibility simultaneously is crucial. However, joint measurements are technically challenging and current methodologies still face adoption challenges. Here, we present easySHARE-seq, an improvement on SHARE-seq for the simultaneous measurement of ATAC- and RNA-seq in single cells. We address several limitations of the previous method by improving the barcode and streamlining the protocol. As a result, easySHARE-seq libraries have a usable sequence of up to 300 bp (+200 bp increase), making it suitable for, e.g., investigation of allele-specific signals or variant discovery. Furthermore, easySHARE-seq libraries do not require a dedicated sequencing run thus saving costs. We applied easySHARE-seq to murine liver nuclei and recovered 19,664 nuclei with joint chromatin and expression profiles. By benchmarking against other combinatorial indexing-based techniques, we showed that we can recover over 1.5-fold more transcripts per cell while retaining high scalability and low cost. To showcase our method, we identified cell types, exploited the multiomic measurements to link cis-regulatory elements to their target genes and investigated liver-specific micro-scale changes. We conclude that easySHARE-seq improves upon previous methods and can produce high-quality multiomic datasets. We expect it to be applicable to a wide range of study designs.

Paternal over- and under-nutrition programme fetal and placental development in a sex-specific manner in mice

a.watkins@sheffield.ac.uk (A Augusto Coppi) — Mon, 20 Jul 2026 00:00:00 +0000

The association between sub-optimal paternal diet and offspring well-being is becoming established. However, the underlying mechanisms are yet to be fully defined. The aim of this study was to establish the impact of over- and under-nutrition, with or without macronutrient supplementation, on male reproductive fitness and post-fertilisation development. Male C57BL/6J mice were fed either control diet (CD), isocaloric low-protein diet (LPD), high-fat/sugar ‘Western’ diet (WD), or LPD or WD supplemented with methyl donors and carriers (MD-LPD or MD-WD, respectively) for 8 weeks before mating with virgin C57/BL6J females. Placental tissue was collected at embryonic day (E)8.5 to assess early placental (ectoplacental cone) morphology and metabolism and E17.5 for sex-specific transcriptomic profiling. Post-mating, stud male tissues were harvested for the assessment of testicular morphology and gene expression, gut microbiota composition, and metabolic status. WD and MD-WD males displayed increased adiposity, hepatic cholesterol and free fatty acids, and gut microbiota dysbiosis when compared to CD-fed males. In the testes, WD and MD-WD perturbed the expression of genes associated with metabolism and transcription regulation. Additionally, we observed differential expression of multiple genes within the Wnt signalling pathway, central in the regulation of cellular proliferation, migration, survival, and cell fate determination during development. Despite no impact on fundamental male fertility, significant changes in ectoplacental cone metabolism, fetal growth, and placental gene expression were observed in response to specific dietary regimens. Interestingly, while CD male and female placentas displayed 301 genome-wide, sexually dimorphic genes, LPD, MD-LPD, WD, and MD-WD male and female placentas possessed only 13, 0, 14, and 15 sexually dimorphic genes, respectively. Our data show that while sub-optimal paternal diet has minimal impact on male fertility, fetal and placental development are perturbed in a sex-specific manner.

Correction: Control of Arabidopsis shoot stem cell homeostasis by two antagonistic CLE peptide signalling pathways

Tue, 14 Jul 2026 00:00:00 +0000

The microtubule-binding protein EML3 is required for mammalian embryonic growth and cerebral cortical development, and Eml3 null mice are a model of cobblestone brain malformation

isabelle.carrier@mail.mcgill.ca (Albert M Berghuis) — Thu, 09 Jul 2026 00:00:00 +0000

The cerebral cortex is a multi-layered structure generated through the migration of neural precursors from their birthplace in the ventricular zone to their destination within the cortical plate. Neuronal migration defects are responsible for many human pathologies collectively called neuronal migration disorders, which include subcortical band heterotopia and cobblestone brain (COB) malformation. One example of a protein involved in a neuronal migration disorder is the echinoderm microtubule-associated protein-like 1 (EML1) protein, one of six members of the mammalian EML family. Absence of EML1 protein results in subcortical band heterotopia in mice and humans. Here, we report that the absence of the paralogous protein EML3 leads to delayed embryonic development and small size, and a COB-like phenotype with neuronal ectopias in the dorsal telencephalon. We found that EML3 is expressed in the neuroepithelium and meningeal mesenchyme when those tissues participate in pial basement membrane (PBM) formation. Transmission electron microscopy demonstrated that the extracellular matrix of the PBM is structurally abnormal in Eml3 null mice when the first radially migrating neurons arrive. The reduced structural integrity of the PBM leads to focal over-migration of neurons into the subarachnoid space. These findings strengthen the link between the EML protein family and cortical neuronal migration defects by identifying Eml3 as the first EML family member whose absence leads to over-migration of neuroblasts. Moreover, we report the first COB-like phenotype with PBM structural defects when a single microtubule-associated protein is deleted.

Arrayed single-gene perturbations identify drivers of human anterior neural tube closure

roya_huang@berkeley.edu (Chudi Abraham-Igwe) — Tue, 07 Jul 2026 00:00:00 +0000

Genetic studies of human embryonic morphogenesis are constrained by ethical and practical challenges, restricting insights into developmental mechanisms and disorders. Human pluripotent stem cell (hPSC)-derived organoids provide a powerful alternative for the study of embryonic morphogenesis. However, screening for genetic drivers of morphogenesis in vitro has been infeasible due to organoid variability and the high costs of performing scaled tissue-wide single-gene perturbations. By overcoming both these limitations, we developed a platform that integrates reproducible organoid morphogenesis with uniform single-gene perturbations, enabling high-throughput arrayed CRISPR interference screening in hPSC-derived organoids. To demonstrate the power of this platform, we screened 77 transcription factors in an organoid model of anterior neurulation to identify ZIC2, SOX11, and ZNF521 as essential regulators of neural tube closure. We discovered that ZIC2 and SOX11 are required for closure, while ZNF521 prevents ectopic closure points. Single-cell transcriptomic analysis of perturbed organoids revealed co-regulated gene targets of ZIC2 and SOX11 and an opposing role for ZNF521, suggesting that these transcription factors jointly govern a gene regulatory program driving neural tube closure in the anterior forebrain region. Our single-gene perturbation platform enables high-throughput genetic screening of in vitro models of human embryonic morphogenesis.

Desert Hedgehog mediates stem Leydig cell differentiation through Ptch2/Gli1/Sf1 signaling axis

wdeshou@swu.edu.cn (Changle Zhao) — Mon, 29 Jun 2026 00:00:00 +0000

Desert Hedgehog (Dhh) mutations cause Leydig cell dysfunction, yet the mechanisms governing Leydig lineage commitment through Dhh-mediated receptor selectivity, transcriptional effector specificity, and steroidogenic coupling remain elusive. In this study, using CRISPR/Cas9-mediated gene knockout and stem Leydig cells (SLCs) transplantation, we identified a critical Dhh/Patched 2 (Ptch2)/Glioma-associated oncogene homolog 1 (Gli1)/steroidogenic factor 1 (Sf1) signaling axis essential for SLC differentiation in Nile tilapia (Oreochromis niloticus). Dhh deficiency resulted in defective adult Leydig cells and androgen insufficiency. Rescue experiments involving 11-ketotestosterone administration and a Dhh agonist treatment, combined with SLCs transplantation, demonstrated that Dhh regulates SLC differentiation, not survival. In vitro knockout of ptch1 and ptch2 in SLCs revealed that Ptch2 likely acts as the functional receptor for Dhh. This was further supported by in vivo genetic rescue experiments, where ptch2 mutation did not impair testicular development, yet completely rescued the testicular defects in dhh mutants—consistent with Ptch2 acting as an inhibitory receptor whose loss alleviates Dhh pathway suppression. Luciferase assays in Gli-knockout SLCs demonstrated that Gli1 acts as the primary transcriptional effector and transactivates sf1 expression. Additionally, functional transplantation assays confirmed that Sf1 is indispensable for SLC differentiation, as Sf1-overexpressing SLCs rescued differentiation, whereas sf1-mutant SLCs failed. Overall, our work delineates the Dhh-Ptch2-Gli1-Sf1 axis and provides fundamental insights into the endocrine regulation of Leydig cell lineage development.

Correction: Generation of a transparent killifish line through multiplex CRISPR/Cas9mediated gene inactivation

Fri, 26 Jun 2026 00:00:00 +0000

A cell atlas of the developing human outflow tract of the heart and its adult aortic valve derivatives

simon.bamforth@newcastle.ac.uk (Andrew D Sharrocks) — Thu, 25 Jun 2026 00:00:00 +0000

The outflow tract (OFT) of the heart carries blood away from the heart into the great arteries. During embryogenesis, the OFT divides to form the aorta and pulmonary trunk, creating the double circulation present in mammals. Defects in this area account for one-third of all congenital heart defect cases. Here, we present comprehensive transcriptomic data on the developing OFT at two distinct time points (embryonic and fetal) and its adult derivatives, the aortic valves, and use spatial transcriptomics to define the distribution of cell populations. We uncover that distinctive embryonic signatures persist in adult cells and can be used as labels to retrospectively attribute relationships between cells separated by a large timescale. Single-cell regulatory network inference identifies GATA6, a transcription factor linked to common arterial trunk and bicuspid aortic valve, as a key regulator of valve precursor cells. Its downstream network reveals candidate drivers of human cardiac defects and illuminates the molecular mechanisms of both normal and pathological valve development. Our findings define the cellular and molecular signatures of the human OFT and its distinct cell lineages, which is critical for understanding congenital heart defects and developing cardiac tissue for regenerative medicine.

The NTR/prodrug revolution: Tools for controlling cell loss and regeneration

mparson1@uci.edu (Gha-Hyun J Kim) — Fri, 05 Jun 2026 00:00:00 +0000

Here, we review the history, advancements, and broad utility of the NTR/prodrug system, and suggest future strategies for developing versatile ablation models. As a chemogenetic tool, the nitroreductase (NTR)/prodrug system enables precise spatiotemporal control over cell ablation. The technology leverages bacterial NTR enzymes (e.g. nfsB) to convert inert prodrugs into cytotoxic agents, thereby allowing researchers to induce targeted cell death. Although the NTR/prodrug approach was first implemented in transgenic mice, it was subsequently adapted to zebrafish, where it has been extensively optimized and applied. Consequently, zebrafish remain the primary focus of this review. Nevertheless, the utility of the NTR/prodrug system has expanded to other important model organisms, including Drosophila, Nematostella, Xenopus, medaka, and rats, enabling detailed studies of tissue damage and regeneration. This review highlights how the NTR system has been deployed to model a spectrum of human diseases, including Parkinson’s disease, retinal degeneration, demyelinating disorders, and kidney disease. These models provide valuable platforms to study pathogenesis in vivo. Furthermore, the precise and controllable nature of NTR ablation makes it an ideal tool for high-throughput chemical and genetic screens aimed at discovering pro-regenerative and protective compounds. The development of NTR2.0, an enzyme variant with over 100-fold greater activity, along with more potent prodrugs such as ronidazole (RNZ), has dramatically broadened experimental possibilities. These improvements permit chronic ablation and long-term disease modeling at well-tolerated drug concentrations. Here, we present some key considerations, including transgenic design for optimal cell-type specificity, calibrating expression levels for desired ablation kinetics, and suitable controls to allow interpretation. These best practices will allow the researcher to develop a precise, reproducible, and versatile platform for either modeling human disease or dissecting regenerative mechanisms.

HSD17B7 is required for the function of sensory hair cells by regulating cholesterol synthesis

ntuwx@ntu.edu.cn (Dong Liu) — Wed, 03 Jun 2026 00:00:00 +0000

Cholesterol homeostasis is fundamental to cellular function, and its disruption underlies a wide range of human diseases. However, the contribution of cholesterol biosynthesis to auditory physiology remains poorly understood. HSD17B7 (17β-Hydroxysteroid dehydrogenase type 7) catalyzes the conversion of zymosterone to zymosterol, a key step in the post-lanosterol cholesterol biosynthetic pathway. Here, we found that Hsd17b7 is highly enriched in sensory hair cells of zebrafish and mice. The deficiency of Hsd17b7 reduced intracellular cholesterol levels in HEI-OC1 cells and zebrafish hair cells, thereby compromising MET and acoustic startle responses. A heterozygous nonsense variant (c.544G>T; p.E182*) in HSD17B7 was identified in an individual with bilateral profound hearing loss. mRNA of c.544G>T HSD17B7 failed to rescue the impaired MET and acoustic startle response of hsd17b7 mutants. Mechanistically, the mutation decreases mRNA abundance and significantly reduces protein. Moreover, expression of the p.E182* mutation disrupted the interaction between HSD17B7 and the ER retention receptor RER1, leading to aberrant subcellular localization and altered cholesterol distribution, thereby exacerbating HC dysfunction. Together, our findings suggest a conserved and essential role for HSD17B7-mediated cholesterol biosynthesis in sensory hair cell function and identify HSD17B7 as a candidate gene for sensorineural hearing loss.

Mural cells protect the adult brain from hemorrhage but do not control the blood–brain barrier in developing zebrafish

oguzhan.baltaci@petermac.org (Alison Farley) — Mon, 01 Jun 2026 00:00:00 +0000

The blood–brain barrier (BBB) protects the brain from circulating metabolites and plays central roles in neurological diseases. Endothelial cells (ECs) of the BBB are enwrapped by mural cells including pericytes and vascular smooth muscle cells (vSMCs) that regulate angiogenesis, vessel stability and barrier function. To explore mural cell control of the BBB, we investigated neurovascular phenotypes in zebrafish pdgfrb mutants that lack brain pericytes and vSMCs. As expected, mutants showed an altered cerebrovascular network with mispatterned capillaries. Unexpectedly, mutants displayed no BBB leakage at larval stages of development. This suggests that pericytes and vSMCs are not essential for normal BBB function in developing zebrafish. Instead, we observed juvenile and adult BBB disruption occurring at ‘hotspot’ focal hemorrhages at large vessel aneurysms. ECs at leakage hotspots showed induction of caveolae on abluminal surfaces and structural defects including basement membrane thickening and disruption. Our work suggests that capillary pericytes primarily regulate cerebrovascular patterning in development and vSMCs of major arteries protect from hemorrhage and BBB breakdown in older zebrafish. The fact that young zebrafish have a functional BBB in the absence of mural cells calls for renewed interrogation of mural cell control of the BBB throughout vertebrate evolution.