bims-cebooc 2026-07-05 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2026–07–05
thirteen papers selected by
Gabriele Zaffagnini, Universität zu Köln

LH stimulates a rapid cAMP-mediated, gap junction-dependent activation of PDE3A in oocytes.
Phenotyping of post-fertilization sperm mitophagy determinants discovered in a mammalian gamete-based cell-free system.
Mouse offspring conceived by in vitro fertilization exhibit accelerated reproductive aging through early ovarian failure.
A mammalian-specific domain of MSH5 drives the transition from crossover licensing to designation during meiotic prophase I.
Boundary geometry controls a topological defect transition that determines lumen nucleation in embryonic development.
Maternal hyperhomocysteinemia compromises female offspring fertility through overactivation of primordial follicles.
Meiosis-Specific Cohesin in Mammalian Germ Cells.
Microtubule stiffening by the doublecortin-domain protein ZYG-8 contributes to mitotic spindle orientation during zygote division in Caenorhabditis elegans.
The Drosophila ovarian terminal filament imports lipophilic molecules that support cyst and follicle development within the ovariole.
High-sensitive glycomics using seGRAP-mass spectrometry uncovers a conserved N-glycome in single human oocytes.
Cumulus Expansion and Oocyte Quality Across the Pubertal Transition in Mice: Implications for Modeling Fertility Preservation in Adolescents.
A Designed Ankyrin Repeat Protein (DARPin) Targeting EGFR Inhibits Ovulation and Enables a Novel Platform for Studying Ovarian Biology and Pathophysiology.
A cell size-dependent competition between geometry and polarity governs nuclear and spindle positioning in early embryos.

Sci Rep. 2026 Jul 02.

LH stimulates a rapid cAMP-mediated, gap junction-dependent activation of PDE3A in oocytes.

Eran Gershon, Iris Maimon, Michal Elbaz, Dalia Galiani, Nava Dekel.

  A major regulator of the intraoocyte levels of cAMP is the cGMP-inhibited PDE3A. This oocyte-specific PDE hydrolyses cAMP, counterbalancing its autonomous GPR3 production and gap junctional transfer from the follicle soma. The pituitary luteinizing hormone (LH) induces resumption of meiosis by reducing the somatic cGMP, which in concomitance with closure of gap junctions lowers its availability to the oocyte. Nevertheless, unlike cGMP, LH elevates the follicle cAMP. This apparent paradox questions whether and how the somatic cAMP elevation serves reinitiation of meiosis. To challenge this intriguing option, we used rat ovarian follicle clusters and cumulus-enclosed/cumulus-free, fully-grown oocytes. The oocytes were incubated with dbcAMP to elevate their cAMP. Follicles were incubated with LH to induce resumption of meiosis. Participation of NO-iNOS pathway was evaluated by either the NO-donor, SNAP or the iNOS inhibitor AG, and involvement of cGMP by a selective sGC inhibitor, ODQ. At the end of incubations, PDE3A activity as well as cAMP concentrations within oocytes were determined. We detected a LH-induced immediate elevation of intra-oocyte cAMP, followed by PKA-mediated activation of PDE3A. Both events were depended on open gap junctions. At this time window, the LH-induced decrease in granulosa-cells NO production followed by reduction in cGMP contributed to the relief of PDE3A inhibition. The later termination of cell-to-cell communication backed a sustained PDE3A activity by stopping the transfer of both, cAMP and cGMP. Our present study suggests that the transient increase in intraoocyte cAMP, which activates the oocyte PDE3A, may serve as a complementary mechanism, to increase the efficiency of LH-induced oocyte maturation.

Keywords:  CAMP; CGMP; INOS; LH; Meiosis; Oocyte maturation; PDE3A

DOI:  https://doi.org/10.1038/s41598-026-59161-y
Biol Res. 2026 Jun 29.

Phenotyping of post-fertilization sperm mitophagy determinants discovered in a mammalian gamete-based cell-free system.

Alexis Jones, Natálie Zelenková, Erica Mantle, Chloe Gardner, Barbora Klusáčková, Dalen Zuidema, Miriam Sutovsky, Pavla Postlerová, Michal Zigo, Peter Sutovsky.

  The targeted, substrate-specific degradation of paternal mitochondria inside the zygote, known as post-fertilization sperm mitophagy, is a crucial and evolutionarily conserved early embryonic event. It ensures the exclusive maternal inheritance of the mitochondrial genome. Post-fertilization sperm mitophagy was initially thought to only be achieved via the ubiquitin-proteasome system. Until pro-autophagic receptor proteins such as SQSTM1, GABARAP, as well as the proteasome-interacting ubiquitinated protein dislocase VCP, were identified as contributors to the degradation of the sperm mitochondria early after mammalian fertilization. This synergy of proteasomal and autophagic pathways ensures a timely degradation of sperm mitochondria shortly after fertilization. The discovery of these autophagic receptors lead researchers to believe there might be other autophagic receptors and determinants necessary for proper post-fertilization sperm mitophagy. Based on the established inventory of proteins from mass spectrometry trials of boar spermatozoa exposed to porcine oocyte extracts in an intra-specific porcine cell-free system (CFS), five candidate mitophagy determinants were further investigated in this study, namely LACTB, PRDX3, PSMA8, TOMM34, and FUNDC1. These proteins of interest were studied and validated by using in vitro fertilization (IVF) protocols, cell imaging of spermatids, spermatozoa, oocytes and zygotes, protein interactome analysis, and the porcine CFS. The proteins PSMA8 and TOMM34 behaved in accordance with our proteomic study predictions. The PSMA8 labeling increased after exposure to CFS; in agreement with the classification PSMA8 was given from the mass spectrometry findings. TOMM34 underwent a visible decrease in labeling after exposure to CFS, which also agreed with its proteomic classification; this labeling persisted in IVF zygotes. Except for LACTB, the examined proteins showed mutual interactions as well as interactions with previously identified sperm mitophagy factors in the STRING interactome analysis. Results from this study validate the novel porcine CFS as a valuable tool for the exploration of early fertilization events at a molecular level. Future phenotyping and functional studies using porcine CFS will advance the understanding of mitochondrial inheritance and zygotic development and potentially shed light on the origins of certain mitochondrial diseases arising from the failure of post-fertilization sperm mitophagy.

Keywords:  Autophagy; Fertilization; Inheritance; Mitochondria; Sperm; Zygote

DOI:  https://doi.org/10.1186/s40659-026-00713-x
J Clin Invest. 2026 Jun 30. pii: e201633. [Epub ahead of print]

Mouse offspring conceived by in vitro fertilization exhibit accelerated reproductive aging through early ovarian failure.

Eric A Rhon-Calderon, Cassidy N Hemphill, Alexandra J Savage, Ana Domingo-Muelas, Zhengfeng Liu, Christopher J Krapp, Laren Riesche, Nicolas Plachta, Richard M Schultz, Marisa S Bartolomei.

  Reproductive aging is characterized by a progressive decline of reproductive function, with broad implications for overall health and longevity. Environmental factors, including assisted reproductive technologies (ART), can accelerate reproductive aging by promoting premature ovarian failure in females. In vitro fertilization (IVF) though widely used and generally considered safe, has been associated with lasting effects on offspring health. Using a mouse model that closely approximates human IVF, we demonstrated that IVF accelerates reproductive aging in female offspring by inducing premature ovarian failure. IVF-conceived females exhibited altered ovarian function, reduced follicle reserve, disrupted endocrine profiles, and transcriptomic and epigenetic changes consistent with premature reproductive decline. These findings reveal long-term consequences of IVF on female reproductive health and highlight the need to understand how early-life interventions influence reproductive longevity.

Keywords:  Development; Embryonic development; Epigenetics; Reproductive biology; Transcriptomics

DOI:  https://doi.org/10.1172/JCI201633
bioRxiv. 2026 Jun 18. pii: 2026.06.16.731784. [Epub ahead of print]

A mammalian-specific domain of MSH5 drives the transition from crossover licensing to designation during meiotic prophase I.

Ky'ara D Carr, Eliza O'Donnell, Tegan S Horan, Maame Serwaa Adjei-Boadu, Anna J Wood, Yongwei Zhang, Winfried Edelmann, Maria de Las Mercedes Carro, Paula E Cohen.

Meiotic recombination initiates with DNA double-strand breaks (DSBs) repaired as either crossovers (COs) or non-crossovers. Across eukaryotes, MSH4/MSH5 (MutSγ) licenses DSB repair intermediates, directing repair into the class I CO pathway via recruitment of MLH1/MLH3 (MutLγ). In mammals, excess MutSγ sites relative to final MutLγ foci suggest additional MutSγ functions, including directing repair through the minor class II CO pathway. We investigated the role of a mammalian-specific 38-amino acid C-terminal domain of MSH5 using mice lacking this domain ( Msh5 ΔC/ΔC ). Spermatocytes and oocytes load MSH4 normally to achieve CO licensing in zygonema, but these numbers decline precipitously in pachynema, leading to dramatically reduced MutLγ foci and associated pro-CO factors HEI10 and CNTD1. Despite this, licensing factors RNF212B and MutSγ-associated kinase CDK4 remain persistently upregulated in pachynema. Strikingly, the switch from licensing-associated CDK4 to CO-site-associated CDK2 fails to occur in Msh5 ΔC/ΔC mice, even at residual class I CO events. The result is rapid germ cell death prior to prophase I completion in both sexes. Thus, the loss of the MSH5 C-terminus functionally uncouples the regulatory proteins that define the stepwise patterning of class I COs. Our findings reveal novel early roles for the C-terminus of mammalian MSH5 in converting licensed DSB repair intermediates to designated class I COs.

DOI: https://doi.org/10.64898/2026.06.16.731784
Nat Mater. 2026 Jul;25(7): 1278-1287

Boundary geometry controls a topological defect transition that determines lumen nucleation in embryonic development.

Pamela C Guruciaga, Takafumi Ichikawa, Steffen Plunder, Takashi Hiiragi, Anna Erzberger.

Topological defects determine the collective properties of anisotropic materials. Nonetheless, it is not fully understood how their configurations are controlled, especially in three dimensions. In living matter, contributions of two-dimensional topological defects to biological functions have been demonstrated, but whether three-dimensional polar defects have any biological relevance is unclear. Here we report a charge-preserving transition between three-dimensional defect configurations driven by boundary geometry and independent of material parameters. Moreover, we find that three-dimensional polar defects in the mouse embryo are the sites where fluid-filled lumina form, essential structures for subsequent development. We validate these findings by experimentally perturbing embryo shape beyond the transition point, which results in the creation of additional lumen initiation sites near predicted defect locations. Overall, our results reveal how boundary geometry controls polar defects, and how embryos use this mechanism for shape-dependent lumen formation. We expect this defect-control principle to apply broadly to systems with orientational order.

DOI: https://doi.org/10.1038/s41563-026-02594-7
iScience. 2026 Jul 17. 29(7): 116393

Maternal hyperhomocysteinemia compromises female offspring fertility through overactivation of primordial follicles.

Jinmei Gao, Lu Wang, Jie Ma, Jialing Li, Yajie Wang, Jinfang Wang, Rong Hu.

  Hyperhomocysteinemia (HHcy), characterized by plasma homocysteine concentrations exceeding 15 μmol/L, has been associated with various issues that impact personal health and offspring well-being. This study examines the effect of maternal HHcy induced by a high-methionine diet on the fertility of female offspring mice. The results showed that maternal HHcy caused the overactivation of primordial follicles in female offspring mice by promoting the phosphorylation of key factors, including RPS6, mTOR, FOXO3a, and AKT. Moreover, the number of mitochondria in mature oocytes decreases, and mitochondrial function decreases, further leading to increased reactive oxygen species (ROS) levels, a higher degree of DNA damage, and spindle abnormalities, ultimately impairing the quality of oocytes. These findings demonstrate that maternal HHcy decreases offspring fertility by inducing primordial follicle overactivation and impairing oocyte quality, providing new insights into the pathological mechanisms through which HHcy affects the reproductive potential of offspring.

Keywords:  developmental biology; female reproductive endocrinology; molecular biology

DOI:  https://doi.org/10.1016/j.isci.2026.116393
Biol Reprod. 2026 Jun 27. pii: ioag134. [Epub ahead of print]

Meiosis-Specific Cohesin in Mammalian Germ Cells.

Kei-Ichiro Ishiguro, Yasuhiro Fujiwara.

  Meiosis requires specialized mechanisms to coordinate chromosome pairing, recombination, and stepwise chromosome segregation. Central to these processes are cohesin complexes that incorporate meiosis-specific subunits, including SMC1β, REC8, RAD21L, and STAG3. Unlike canonical mitotic cohesin, these variants endow germ cells with distinct regulatory properties that ensure durable sister chromatid cohesion, promote homolog interactions, and establish the unique segregation patterns of meiosis I and II. Genetic and cytological studies have revealed that individual kleisin subunits perform non-redundant functions: REC8 provides the primary replication-coupled cohesion essential for chromosome axis integrity, whereas RAD21L supports homolog pairing and recombination through mechanisms linked to double-strand break formation. At centromeres, protected cohesin complexes cooperate with shugoshin-PP2A to preserve cohesion and define kinetochore orientation, thereby enabling reductional division. A remarkable feature of mammalian oocytes is the extraordinary longevity of meiotic cohesin, which must be maintained for years to decades without efficient turnover. Age-dependent deterioration of this cohesion machinery represents a major source of chromosome mis-segregation, contributing to infertility, miscarriage, and congenital aneuploidies. In this Review, we focus on the molecular composition, regulation, and functional specialization of meiosis-specific cohesins in mammalian germ cells. We integrate recent genetic, biochemical, and imaging studies to discuss how distinct cohesin complexes partition tasks during prophase, how cohesion is protected at centromeres, and how cohesin failure underlies reproductive aging and disease.

Keywords:  Chromosome Axis; Chromosome segregation; Cohesin; Meiosis; aneuploidy; sister chromatid cohesion

DOI:  https://doi.org/10.1093/biolre/ioag134
PLoS Genet. 2026 Jun 29. 22(6): e1012196

Microtubule stiffening by the doublecortin-domain protein ZYG-8 contributes to mitotic spindle orientation during zygote division in Caenorhabditis elegans.

Louis Cueff, Loïc Schmitt, Ewen Huet, Sylvain Pastezeur, Méline Coquil, Talia Savary, Anouk Sénard, Jacques Pécréaux, Hélène Bouvrais.

In the Caenorhabditis elegans zygote, mutations in zyg-8DCLK1, the sole Doublecortin-family member, disrupt mitotic spindle positioning, as seen by immunofluorescence. Doublecortin proteins bind microtubules and are thought to stabilise or rigidify them. In the zygote, ZYG-8 only modestly affects microtubule growth and nucleation. We thus investigated whether these moderate dynamic perturbations alone could explain the spindle mispositioning observed in zyg-8 mutants. Using three complementary genetic perturbations-RNAi-mediated depletion of ZYG-8, its overexpression, and the thermosensitive zyg-8(or484ts) mutant (that disrupts microtubule binding)-we observed altered spindle pole oscillations and changes in microtubule cortical-contact behaviour, indicative of impaired cortical forces. Importantly, these phenotypes could not be fully explained by previously reported alterations in microtubule dynamics, suggesting an additional mechanism. Our findings indicate that ZYG-8 increases microtubule rigidity: ZYG-8 depletion or mutation led to more frequent microtubule bending and higher curvature and tortuosity. Simulations confirmed that reduced rigidity prolongs cortical contact lifetimes, an effect we experimentally observed in zyg-8(RNAi) embryos. Using custom biophysical assays, we showed that microtubule softening in zyg-8(RNAi) embryos and zyg-8 mutants reduced the efficiency of centring forces, leading to exaggerated spindle-pole oscillations. In mutants, the largest oscillations caused spindle poles to move closer to the cell periphery, preventing re-centring and resulting in spindle mispositioning and misorientation during late anaphase. Importantly, reducing cortical pulling forces rescued orientation defects, highlighting the importance of balanced pulling-pushing forces for proper spindle positioning. We propose that sufficient microtubule rigidity is essential for generating effective cortical pushing forces, potentially in synergy with other microtubule properties, which contribute to centring mechanisms that ensure accurate spindle orientation in late mitosis. Given that DCLK1 is frequently deregulated in human cancers and that accurate spindle positioning is essential for maintaining cell proliferation-differentiation balance, these findings may have implications for understanding how disruptions in microtubule mechanics contribute to carcinogenesis.

DOI: https://doi.org/10.1371/journal.pgen.1012196
Dev Biol. 2026 Jun 30. pii: S0012-1606(26)00138-7. [Epub ahead of print]

The Drosophila ovarian terminal filament imports lipophilic molecules that support cyst and follicle development within the ovariole.

Bhawana Maurya, Allan C Spradling.

  Oogenesis in Drosophila requires small molecules as biosynthetic precursors and regulators of follicle development. But how such molecules reach germline stem cells (GSCs), developing germline cysts and follicles in the germarium and early ovariole is poorly understood. The flat, stacked cells of the terminal filament (TF) form a specialized somatic structure positioned at the anterior end of ovarioles in virtually all insect ovaries, but physiological roles TFs play in adult ovaries remain little known. By briefly knocking down, specifically in the TF, exocyst components affecting vesicle trafficking, lipid importers such as LpR2, and organic anion importers such as Oatp30B, we found that the TF provides lipophilic molecules to GSCs and downstream germarium cells needed to maintain lipid droplets, and germ cell differentiation. When exocyst component Sec6 is knocked down, vesicles containing lipophilic cargos back up at the TF-germ cell junction, suggesting that endosomes move between the stacked TF cells and into cap cells by transcytosis. Our studies suggest that TFs import lipophilic precursors and regulators to autonomously coordinate their ovariole's stem cell activity and cyst development.

Keywords:  Oatp30B; exocyst; germline stem cell; ovariole; stem cell niche

DOI:  https://doi.org/10.1016/j.ydbio.2026.06.013
Nat Commun. 2026 Jul 03. pii: 5836. [Epub ahead of print]17(1):

High-sensitive glycomics using seGRAP-mass spectrometry uncovers a conserved N-glycome in single human oocytes.

Nafisa Tursumamat, Qiannan Liu, Jihong Lu, Shuhong Guo, Shuangshuang Du, Shengyang Liu, Shuye Wu, Heming Li, Peng Wu, Bin Li, Juan Wei.

High-sensitivity glycomic analysis is essential for advancing both basic and translational biomedical research, yet remains methodologically challenging for limited-quantity samples, primarily due to complex workflows and reliance on specialized instrumentation. Here, we introduce solution-enhanced glycan reduction and permethylation (seGRAP), a streamlined, accessible, and high-sensitive method that enables glycan profiling from sub-nanogram protein inputs and picoliter-scale human plasma using widely available mass spectrometry (MS) platforms. seGRAP-MS demonstrates consistently robust and reproducible glycomic performance and enables comprehensive N-glycome characterization of human oocytes at single-cell resolution. Our single-oocyte analysis uncovers a highly conserved N-glycome across both individuals and developmental stages, revealing a previously uncharacterized layer of molecular stability in human reproduction. By significantly lowering technical and logistical barriers, seGRAP-MS redefines the benchmark for high-sensitive glycomics, expanding accessibility and empowering broader applications in fundamental biology, clinical research, and precision medicine.

DOI: https://doi.org/10.1038/s41467-026-73050-y
Res Sq. 2026 Jun 24. pii: rs.3.rs-9658129. [Epub ahead of print]

Cumulus Expansion and Oocyte Quality Across the Pubertal Transition in Mice: Implications for Modeling Fertility Preservation in Adolescents.

Dilan Gokyer, Luhan T Zhou, Sophia Akinboro, Elnur Babayev.

OBJECTIVE: To determine whether cumulus expansion and oocyte aneuploidy differ across the pubertal transition in a murine model designed to approximate clinical assisted reproductive technology (ART) conditions.
METHODS: Controlled experimental animal study using prepubertal (D16-25), peripubertal (D26-35), and reproductively young adult CD-1 female mice (9 and 12 weeks old). Mice underwent gonadotropin stimulation to model controlled ovarian hyperstimulation. Cumulus-oocyte complexes (COCs) were collected following in vivo maturation prior to ovulation or assessed before and after in vitro maturation (IVM). Main outcome measures included COC surface area, cumulus cell layer thickness, oocyte spindle configuration, chromosome alignment, and aneuploidy rates.
RESULTS: Following in vivo maturation, COC surface area (1505 ± 151.4 µm² vs. 1735 ± 115.7 µm² vs. 1637 ± 75.6 µm², p = 0.44), cumulus layer thickness (176 ± 18 µm vs. 201.5 ± 21.2 µm vs. 196.7 ± 13.7 µm, p = 0.59), and oocyte euploidy rates (94.25 ± 3.6% vs. 91.41 ± 4.8% vs. 88.14 ± 2.9%, p = 0.57) were similar across D21-25, D28-35, and 12-week cohorts, respectively. Under IVM conditions, pre-IVM COC area was smaller in D16-21 mice compared with 9-week mice (377.6 ± 5.6 µm² vs. 466.8 ± 16.5 µm², p < 0.05). However, post-IVM COC area, cumulus expansion, and spindle/chromosome abnormality rates did not differ among groups (all p > 0.05).
CONCLUSION: In this murine model, markers of oocyte competence, including cumulus expansion, meiotic integrity, and aneuploidy rates, were largely preserved across the pubertal transition, highlighting translational limitations of mice for modeling human adolescent ovarian biology.

DOI: https://doi.org/10.21203/rs.3.rs-9658129/v1
bioRxiv. 2026 Jun 26. pii: 2026.06.22.732379. [Epub ahead of print]

A Designed Ankyrin Repeat Protein (DARPin) Targeting EGFR Inhibits Ovulation and Enables a Novel Platform for Studying Ovarian Biology and Pathophysiology.

Yubing Liu, Jiyang Zhang, Shichao Liu, Connie Mitra, Yue Liu, Hannah M VanBenschoten, Brittany Goods, Feng Chen, Shuo Xiao.

Ovarian disorders, including anovulation, primary ovarian insufficiency (POI), and polyendocrine metabolic ovarian syndrome (PMOS), affect millions of reproductive-age women worldwide; however, mechanistic studies of ovarian biology and pathophysiology remain challenging because current experimental approaches often lack selectivity, tunability, or physiological relevance. Genetically modified animal models are labor-intensive and irreversible; small molecules frequently exhibit off-target effects; and conventional antibodies have limited tissue penetration and restricted temporal control. Designed ankyrin repeat proteins (DARPins) represent a highly modular protein engineering platform with advantages in specificity, size, stability, and extracellular targeting, but their utility in reproductive biology remains largely unexplored. Here, we used epidermal growth factor receptor (EGFR)-targeting DARPins as a proof-of-concept platform to interrogate ovarian signaling during ovulation. Screening of engineered anti-EGFR DARPins identified SX-006, a bispecific tetravalent construct with robust cross-species EGFR binding and potent biological activity. Using an ex vivo murine ovulation system, SX-006 inhibited follicle rupture in a dose-dependent manner with IC50 of 1.21 μM without overt cytotoxicity. Lower concentrations of SX-006 preferentially perturbed follicle rupture while largely preserving oocyte meiotic maturation and luteinization, suggesting differential sensitivity of ovulatory processes to extracellular EGFR blockade. Comparative transcriptomic analyses further revealed that extracellular EGFR blockade and small molecule-based intracellular EGFR kinase inhibition produce overlapping but also distinct transcriptional responses, supporting biologically distinct modes of ovulatory signaling pathway perturbation. Together, these findings establish DARPins as a selective, tunable, and physiologically relevant platform for studying ovarian signaling and provide proof-of-concept for extracellular receptor targeting in ovarian biology, infertility research, and non-hormonal contraceptive development.
Summary sentence: An engineered EGFR-targeting DARPin selectively inhibits ovulation through extracellular receptor blockade and establishes a versatile platform for investigating ovarian signaling and reproductive disorders.

DOI: https://doi.org/10.64898/2026.06.22.732379
Curr Biol. 2026 Jul 01. pii: S0960-9822(26)00724-4. [Epub ahead of print]

A cell size-dependent competition between geometry and polarity governs nuclear and spindle positioning in early embryos.

Aude Nommick, Macy Baboch, Celia Municio-Diaz, Jeremy Sallé, Remi Le Borgne, Nicolas Minc.

Nuclei and mitotic spindles are actively positioned at defined locations within cells to regulate cell polarity, division, and multicellular morphogenesis.1,2,3,4 Forces generated by cytoskeleton networks regulate the positioning of these organelles and are commonly influenced by extrinsic cues, such as cell geometry or polarity.5,6,7,8,9,10,11,12 To date, however, most studies have investigated this problem in one given cell type, hampering our understanding of how mechanical systems that position nuclei and spindles may scale during multicellular development. We tracked the spatiotemporal behavior of centrosomes, nuclei, and spindles in early sea urchin embryos from the 1-cell to the ∼1,000-cell blastula stage. We found that they are initially located at cell centers, but that they undergo a progressive decentration toward the embryo apical surface, as cells become smaller during development. This apical shift is mediated by microtubule (MT) pulling forces, which are influenced by both cell shapes and apical polarity domains. Using 3D mathematical models and embryo dissections, we propose that apical cortical polarity MT decentering forces progressively take over centering forces during development as a consequence of cell size reduction and resulting increase in surface-to-volume ratio. Our results support a self-organized scenario in which polarity cues progressively outcompete cell geometry to modulate the overall balance of MT forces and pattern nuclear and spindle positioning throughout early embryo development.

DOI: https://doi.org/10.1016/j.cub.2026.06.013