Biology subjects

Guo, F.

Publications and source records attributed to Guo, F..

At least 127 records · Page 7Linked to original sources

bioRxiv2020

Panoramic Insights into the Microevolution and Macroevolution of Prevotella copri-containing Lineage in Primate Guts

Prevotella copri and related taxa are widely detected in mammalian gut microbiomes and have been linked with one human enterotype. However, their microevolution and macroevolution among hosts are poorly characterized. In this study, extensively collected marker genes and genomes were analyzed to trace their evolutionary history, host specificity, and biogeographic distribution. Investigations based on 16S rRNA gene, gyrB, and genomes suggested that a multi-specific P. copri-containing lineage (PCL) harbors diverse species in higher primates. Firstly, P. copri is the dominant species of PCL in the human gut and consists of multiple groups exhibiting high genomic divergence and conspicuous but non-strict biogeographic pattern. Most African strains with high genomic divergence from other strains were phylogenetically placed near the species root, indicating the co-evolutionary history of P. copri and Homo sapiens. Secondly, although long-term co-evolution between PCL and higher primates was revealed, sporadic signals of co-speciation and extensive host jumping of PCL members were observed among higher primates. Metagenomic and phylogenetic analyses indicated that P. copri and other PCL species found in captive mammals have been recently transmitted from humans. Thirdly, strong evidence was found on the extensively horizontal transfer of genes (e.g., carbohydrate-active enzyme encoding genes) among sympatric P. copri groups and PCL species in the same primate host. Our study provides panoramic insights into the complex effects of vertical and horizontal transmission, and potential niche adaption on speciation, host, and biogeographical distribution spanning microevolutionary and macroevolutionary history for a certain gut bacterial lineage. ImportancePrevotella copri and its related taxa, which we designated as Prevotella copri-containing lineage (PCL) in the present study, are widely detected in guts of human, non-human primates and many captive mammals, showing positive or negative correlation to some human diseases. However, a comprehensive understanding on its microevolutionary (within P. copri) and macroevolutionary (among PCL members) history across host species and host biogeography is still lacking. According to our analysis based on 16S rRNA gene, gyrB and genomes, we provided the panoramic insights into the putative effects of vertical transfer, horizontal transmission and potential niche selection on host and biogeographical distribution of this gut bacterial lineage and P. copri. To our knowledge, it is the first time that a gut bacterial lineage was studied at both micro- and macroevolutionary levels, which can aid our systematic understanding on the host-microbe co-evolutionary interactions.

microbiology↗

bioRxiv2020

Insight into vaccine development for Alpha-coronaviruses based on structural and immunological analyses of spike proteins

Coronaviruses that infect humans belong to the Alpha-coronavirus (including HCoV-229E) and Beta-coronavirus (including SARS-CoV and SARS-CoV-2) genera. In particular, SARS-CoV-2 is currently a major threat to public health worldwide. However, no commercial vaccines against the coronaviruses that can infect humans are available. The spike (S) homotrimers bind to their receptors through the receptor-binding domain (RBD), which is believed to be a major target to block viral entry. In this study, we selected Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) as models. Their RBDs were observed to adopt two different conformational states (lying or standing). Then, structural and immunological analyses were used to explore differences in the immune response with RBDs among these coronaviruses. Our results showed that more RBD-specific antibodies were induced by the S trimer with the RBD in the "standing" state (SARS-CoV and SARS-CoV-2) than the S trimer with the RBD in the "lying" state (HCoV-229E), and the affinity between the RBD-specific antibodies and S trimer was also higher in the SARS-CoV and SARS-CoV-2. In addition, we found that the ability of the HCoV-229E RBD to induce neutralizing antibodies was much lower and the intact and stable S1 subunit was essential for producing efficient neutralizing antibodies against HCoV-229E. Importantly, our results reveal different vaccine strategies for coronaviruses, and S-trimer is better than RBD as a target for vaccine development in Alpha-coronavirus. Our findings will provide important implications for future development of coronavirus vaccines. ImportanceOutbreak of coronaviruses, especially SARS-CoV-2, poses a serious threat to global public health. Development of vaccines to prevent the coronaviruses that can infect humans has always been a top priority. Coronavirus spike (S) protein is considered as a major target for vaccine development. Currently, structural studies have shown that Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) RBDs are in lying and standing state, respectively. Here, we tested the ability of S-trimer and RBD to induce neutralizing antibodies among these coronaviruses. Our results showed that Beta-CoVs RBDs are in a standing state, and their S proteins can induce more neutralizing antibodies targeting RBD. However, HCoV-229E RBD is in a lying state, and its S protein induces a low level of neutralizing antibody targeting RBD. Our results indicate that Alpha-coronavirus is more conducive to escape host immune recognition, and also provide novel ideas for the development of vaccines targeting S protein.

microbiology↗

bioRxiv2020

An enormous Paris polyphylla genome sheds light on genome size evolution and polyphyllin biogenesis

The monocot family Melanthiaceae with varying genome sizes in a range of 230-fold is an ideal model to study the genome size fluctuation in plants. Its family member Paris genus demonstrates an evolutionary trend of bearing huge genomes characterized by an average c-value of 49.22 pg. Here, we report a 70.18 Gb genome assembly out of the 82.55 Gb genome of Paris polyphylla var. yunnanensis (PPY), which represents the biggest sequenced genome to date. We annotate 69.53% repetitive sequences in this genome and 62.50% of which are long-terminal repeat (LTR) transposable elements. Further evolution analysis indicates that the giant genome likely results from the joint effect of common and species-specific expansion of different LTR superfamilies, which might contribute to the environment adaptation after speciation. Moreover, we identify the candidate pathway genes for the biogenesis of polyphyllins, the PPY-specific medicinal saponins, by complementary approaches including genome mining, comprehensive analysis of 31 next-generation RNA-seq data and 55.23 Gb single-molecule circular consensus sequencing (CCS) RNA-seq reads, and correlation of the transcriptome and phytochemical data of five different tissues at four growth stages. This study not only provides significant insights into plant genome size evolution, but also paves the way for the following polyphyllin synthetic biology.

plant biology↗

bioRxiv2020

Structures of microRNA-precursor apical junctions and loops reveal non-canonical base pairs important for processing

Metazoan pri-miRNAs and pre-miRNAs fold into characteristic hairpins that are recognized by the processing machinery. Essential to the recognition of these miR-precursors are their apical junctions where double-stranded stems meet single-stranded hairpin loops. Little is known about how apical junctions and loops fold in three-dimensional space. Here we developed a scaffold-directed crystallography method and determined the structures of eight human miR-precursor apical junctions and loops. Six structures contain non-canonical base pairs stacking on top of the hairpin stem. U-U pair contributes to thermodynamic stability in solution and is highly enriched at human miR-precursor apical junctions. Our systematic mutagenesis shows that U-U is among the most efficiently processed variants. The RNA-binding heme domain of pri-miRNA-processing protein DGCR8 binds longer loops more tightly and non-canonical pairs at the junction appear to modulate loop length. Our study provides structural and biochemical bases for understanding miR-precursors and molecular mechanisms of microRNA maturation.

molecular biology↗

bioRxiv2020

Exploration of target spaces in the human genome for protein and peptide drugs

MotivationProtein and peptide drugs, after decades of development have grown into a major drug class of the marketplace. Target identification and validation is crucial for their discovery, and bioinformatics estimation of candidate targets based on characteristics of successful target proteins will help improve efficiency and success rate of target selection. However, owing to the development history of the pharmaceutical industry, previous systematic exploration of target space mainly focused on traditional small-molecule drugs, whereas that for protein and peptide drugs is blank. Here we systematically explored target spaces in the human genome specially for protein and peptide drugs. ResultsWe found that compared with other proteins, targets of both successful protein and peptide drugs have their own characteristics in many aspects and are also significantly different from those of traditional small-molecule drugs. Further based on these features, we developed effective genome-wide target estimation models respectively for protein and peptide drugs.

bioinformatics↗

bioRxiv2020

A concept shift in the mechanistic understanding of HIFα-regulated developmental myelination

The developing CNS is exposed to physiological hypoxia, under which hypoxia inducible factor alpha (HIF) is stabilized and plays a crucial role in regulating neural development. The cellular and molecular mechanisms of HIF in developmental myelination remain incompletely understood. Previous concept proposes that HIF regulates CNS developmental myelination by activating the autocrine Wnt/{beta}-catenin signaling in oligodendrocyte progenitor cells (OPCs). Here, by analyzing a battery of genetic mice of both sexes, we presented in vivo evidences supporting an alternative understanding of oligodendroglial HIF-regulated developmental myelination. At the cellular level, we found that HIF was required for developmental myelination by transiently controlling upstream OPC differentiation but not downstream oligodendrocyte maturation and that HIF dysregulation in OPCs but not oligodendrocytes disturbed normal developmental myelination. We demonstrated that HIF played a minor, if any, role in regulating canonical Wnt signaling in the oligodendroglial lineage or in the CNS. At the molecular level, blocking autocrine Wnt signaling did not affect HIF-regulated OPC differentiation and myelination. We further identified HIF-Sox9 regulatory axis as an underlying molecular mechanism in HIF-regulated OPC differentiation. Our findings support a concept shift in our mechanistic understanding of HIF-regulated CNS myelination from the previous Wnt-dependent view to a Wnt-independent one and unveil a previously unappreciated HIF-Sox9 pathway in regulating OPC differentiation.

neuroscience↗

bioRxiv2020

Acoustofluidic Assembly of 3D Neurospheroids to Model Alzheimer's Disease

Neuroinflammation plays a central role in the progression of many neurodegenerative diseases such as Alzheimers disease, and challenges remain in modeling the complex pathological or physiological processes. Here, we report an acoustofluidic 3D cell culture device that can rapidly construct 3D neurospheroids and inflammatory microenvironments for modeling microglia-mediated neuroinflammation in Alzheimers disease. By incorporating a unique contactless and label-free acoustic assembly, this cell culture platform can assemble dissociated embryonic mouse brain cells into hundreds of uniform 3D neurospheroids with controlled cell numbers, composition (e.g. neurons, astrocytes, and microglia), and environmental components (e.g. amyloid-{beta} aggregates) in hydrogel within minutes. Moreover, this platform can maintain and monitor the interaction among neurons, astrocytes, microglia, and amyloid-{beta} aggregates in real-time for several days to weeks, after the integration of a high-throughput, time-lapse cell imaging approach. We demonstrated that our engineered 3D neurospheroids can represent the amyloid-{beta} neurotoxicity, which is one of the main pathological features of Alzheimers disease. Using this method, we also investigated the microglia migratory behaviors and activation in the engineered 3D inflammatory microenvironment at a high throughput manner, which is not easy to achieve in 2D neuronal cultures or animal models. Along with the simple fabrication and setup, the acoustofluidic technology is compatible with conventional Petri dishes and well-plates, supports the fine-tuning of the cellular and environmental components of 3D neurospheroids, and enables the high-throughput cellular interaction investigation. We believe our technology may be widely used as in vitro brain models for modeling neurodegenerative diseases, discovering new drugs, and testing neurotoxicity.

bioengineering↗

bioRxiv2020

Video Recording Can Conveniently Assay Mosquito Locomotor Activity

Anopheles gambiae and Aedes aegypti are perhaps the best studied mosquito species and important carriers of human malaria and arbovirus, respectively. Mosquitoes have daily rhythms in behaviors and show a wide range of activity patterns. Although Anopheles is known to be principally nocturnal and Aedes principally diurnal, details of mosquito activity are not easily assayed in the laboratory. We recently described FlyBox, a simple tracking system for assaying Drosophila locomotor activity rhythms and thought that it might also be applicable to monitoring mosquito activity. Indeed, we show here that FlyBox can easily, conveniently, affordably and accurately measure the activity of Anopheles as well as Aedes over several days. The resulting profiles under light-dark as well as constant darkness conditions are compatible with results in the literature, indicating that this or similar systems will be useful in the future for more detailed studies on a range of insect species and under more diverse laboratory conditions.

neuroscience↗

bioRxiv2020

Fe(III) heme sets an activation threshold for processing distinct groups of pri-miRNAs in mammalian cells

The essential biological cofactor heme is synthesized in cells in the Fe(II) form. Oxidized Fe(III) heme is specifically required for processing primary transcripts of microRNAs (pri-miRNAs) by the RNA-binding protein DGCR8, a core component of the Microprocessor complex. It is unknown how readily available Fe(III) heme is in the largely reducing environment in human cells and how changes in cellular Fe(III) heme availability alter microRNA (miRNA) expression. Here we address the first question by characterizing DGCR8 mutants with various degrees of deficiency in heme-binding. We observed a strikingly simple correlation between Fe(III) heme affinity in vitro and the Microprocessor activity in HeLa cells, with the heme affinity threshold for activation estimated to be between 0.6-5 pM under typical cell culture conditions. The threshold is strongly influenced by cellular heme synthesis and uptake. We suggest that the threshold reflects a labile Fe(III) heme pool in cells. Based on our understanding of DGCR8 mutants, we reanalyzed recently reported miRNA sequencing data and conclude that heme is generally required for processing canonical pri-miRNAs, that heme modulates the specificity of Microprocessor, and that cellular heme level and differential DGCR8 heme occupancy alter the expression of distinct groups of miRNAs in a hierarchical fashion. Overall, our study provides the first glimpse of a labile Fe(III) heme pool important for a fundamental physiological function and reveal principles governing how Fe(III) heme modulates miRNA maturation at a genomic scale. We also discuss potential states and biological significance of the labile Fe(III) heme pool.

molecular biology↗

bioRxiv2020

Glial type specific regulation of CNS angiogenesis by HIFα-activated different signaling pathways

The mechanisms by which oligodendroglia modulate CNS angiogenesis remain elusive. Previous in vitro data suggest that oligodendroglia regulate CNS endothelial cell proliferation and blood vessel formation through hypoxia inducible factor alpha (HIF)-activated Wnt (but not VEGF) signaling. Using in vivo genetic models, we show that HIF in oligodendroglia is necessary and sufficient for angiogenesis independent of CNS regions. At the molecular level, HIF stabilization in oligodendroglia does not perturb Wnt signaling but remarkably activates VEGF. At the functional level, genetically blocking oligodendroglia-derived VEGF but not Wnt significantly decreases oligodendroglial HIF-regulated CNS angiogenesis. Interestingly, blocking astroglia-derived Wnt signaling reduces astroglial HIF-regulated CNS angiogenesis. Together, our in vivo data clearly demonstrate that oligodendroglial HIF regulates CNS angiogenesis through Wnt-independent and VEGF-dependent signaling. Our findings represent an alternative mechanistic understanding of CNS angiogenesis by postnatal glial cells and unveil a glial cell type-dependent HIF-Wnt axis in regulating CNS vessel formation.

neuroscience↗

bioRxiv2020

Layer-dependent multiplicative effects of spatial attention on contrast responses in human early visual cortex

Attention mechanisms at different cortical layers of human visual cortex remain poorly understood. Using submillimeter-resolution fMRI at 7T, we investigated the effects of top-down spatial attention on the contrast responses across different cortical depths in human early visual cortex. Gradient echo (GE) T2* weighted BOLD signal showed an additive effect of attention on contrast responses across cortical depths. Compared to the middle cortical depth, attention modulation was stronger in the superficial and deep depths of V1, and also stronger in the superficial depth of V2 and V3. Using ultra-high resolution (0.3mm in-plane) balanced steady-state free precession (bSSFP) fMRI, a multiplicative scaling effect of attention was found in the superficial and deep layers, but not in the middle layer of V1. Attention modulation of low contrast response was strongest in the middle cortical depths, indicating baseline enhancement or contrast gain of attention modulation on feedforward input. Finally, the additive effect of attention on T2* BOLD can be explained by strong nonlinearity of BOLD signals from large blood vessels, suggesting multiplicative effect of attention on neural activity. These findings support that top-down spatial attention mainly operates through feedback connections from higher order cortical areas, and a distinct mechanism of attention may also be associated with feedforward input through subcortical pathway. HighlightsO_LIResponse or activity gain of spatial attention in superficial and deep layers C_LIO_LIContrast gain or baseline shift of attention in V1 middle layer C_LIO_LINonlinearity of large blood vessel causes additive effect of attention on T2* BOLD C_LI

neuroscience↗

bioRxiv2020

One-stop Microfluidic Assembly of Human Brain Organoids to Model Prenatal Cannabis Exposure

Prenatal cannabis exposure (PCE) influences human brain development, but it is challenging to model PCE using animals and current cell culture techniques. Here, we developed a one-stop microfluidic platform to assemble and culture human cerebral organoids from human embryonic stem cells (hESC) to investigate the effect of PCE on early human brain development. By incorporating perfusable culture chambers, air-liquid interface, and one-stop protocol, this microfluidic platform can simplify the fabrication procedure, and produce a large number of organoids (169 organoids per 3.5 cm x 3.5 cm device area) without fusion, as compared with conventional fabrication methods. These one-stop microfluidic assembled cerebral organoids not only recapitulate early human brain structure, biology, and electrophysiology but also have minimal size variation and hypoxia. Under on-chip exposure to the psychoactive cannabinoid, delta-9-tetrahydrocannabinol (THC), cerebral organoids exhibited reduced neuronal maturation, downregulation of cannabinoid receptor type 1 (CB1) receptors, and impaired neurite outgrowth. Moreover, transient on-chip THC treatment also decreased spontaneous firing in microfluidic assembled brain organoids. This one-stop microfluidic technique enables a simple, scalable, and repeatable organoid culture method that can be used not only for human brain organoids, but also for many other human organoids including liver, kidney, retina, and tumor organoids. This technology could be widely used in modeling brain and other organ development, developmental disorders, developmental pharmacology and toxicology, and drug screening.

bioengineering↗

bioRxiv2020

scTPA: A web tool for single-cell transcriptome analysis of pathway activation signatures

The most fundamental challenge in current single-cell RNA-seq data analysis is functional interpretation and annotation of cell clusters. The biological pathways in distinct cell types have different activation patterns, which facilitates understanding cell functions in single-cell transcriptomics. However, no effective web tool has been implemented for single-cell transcriptomic data analysis based on prior biological pathway knowledge. Here, we introduce scTPA (http://sctpa.bio-data.cn/sctpa), which is a web-based platform providing pathway-based analysis of single-cell RNA-seq data in human and mouse. scTPA incorporates four widely-used gene set enrichment methods to estimate the pathway activation scores of single cells based on a collection of available biological pathways with different functional and taxonomic classifications. The clustering analysis and cell-type-specific activation pathway identification were provided for the functional interpretation of cell types from pathway-oriented perspective. An intuitive interface allows users to conveniently visualize and download single-cell pathway signatures. Together, scTPA is a comprehensive tool to identify pathway activation signatures for dissecting single cell heterogeneity.

genomics↗

bioRxiv2019

High Throughput Screening at the Membrane Interface Reveals New Inhibitors of Amyloid-β

Amyloid-{beta} aggregation at the cell-membrane of neruonal cells is implicated as a source of toxicity for Alzheimers disease. Small molecules have been studied for their ability to supress amyloid aggregation and toxicity, but the presence of membranes negate their activity. Here, we have identified 5 small molecules that are active at the membrane interface.

biochemistry↗

bioRxiv2019

Effects of Inaccurate Response Function Calibration on Characteristics of the Fiber Orientation Distribution in Diffusion MRI

Diffusion MRI of the brain enables to quantify white matter fiber orientations noninvasively. Several approaches have been proposed to estimate such characteristics from diffusion MRI data with spherical deconvolution being one of the most widely used methods. Constrained spherical deconvolution requires to define - or derive from the data - a response function, which is used to compute the fiber orientation distribution (FOD). This definition or derivation is not unequivocal and can thus result in different characteristics of the response function which are expected to affect the FOD computation and the subsequent fiber tracking. In this work, we explored the effects of inaccuracies in the shape and scaling factors of the response function on the FOD characteristics. With simulations, we show that underestimation of the shape factor in the response functions has a larger effect on the FOD peaks than overestimation of the shape factor, whereas the latter will cause more spurious peaks. Moreover, crossing fiber populations with a smaller separation angle were more sensitive to the response function inaccuracy than fiber populations with more orthogonal separation angles. Furthermore, the FOD characteristics show deviations as a result of modified shape and scaling factors of the response function. Results with the in vivo data demonstrate that the deviations of the FODs and spurious peaks can further deviate the termination of propagation in fiber tracking. This work highlights the importance of proper definition of the response function and how specific calibration factors can affect the FOD and fiber tractography results.

neuroscience↗

bioRxiv2019

Spherical deconvolution with tissue-specific response functions and multi-shell diffusion MRI to estimate multiple fiber orientation distributions (mFODs)

In diffusion MRI, spherical deconvolution approaches can estimate local white matter (WM) fiber orientation distributions (FOD) which can be used to produce fiber tractography reconstructions. The applicability of spherical deconvolution to grey matter (GM), however, is still limited, despite its critical role as start/endpoint of WM fiber pathways. The advent of multi-shell diffusion MRI data offers additional contrast to model the GM signal but, to date, only isotropic models have been applied to GM. Evidence from both histology and high-resolution diffusion MRI studies suggests a marked anisotropic character of the diffusion process in GM, which could be exploited to improve the description of the cortical organization. In this study, we investigated whether performing spherical deconvolution with tissue specific models of both WM and GM can improve the characterization of the latter while retaining state-of-the-art performances in WM. To this end, we developed a framework able to simultaneously accommodate multiple anisotropic response functions to estimate multiple, tissue-specific, fiber orientation distributions (mFODs). As proof of principle, we used the diffusion kurtosis imaging model to represent the WM signal, and the neurite orientation dispersion and density imaging (NODDI) model to represent the GM signal. The feasibility of the proposed approach is shown with numerical simulations and with data from the Human Connectome Project (HCP). The performance of our method is compared to the current state of the art, multi-shell constrained spherical deconvolution (MSCSD). The simulations show that with our new method we can accurately estimate a mixture of two FODs at SNR[≥]50. With HCP data, the proposed method was able to reconstruct both tangentially and radially oriented FODs in GM, and performed comparably well to MSCSD in computing FODs in WM. When performing fiber tractography, the trajectories reconstructed with mFODs reached the cortex with more spatial continuity and for a longer distance as compared to MSCSD and allowed to reconstruct short trajectories tangential to the cortical folding. In conclusion, we demonstrated that our proposed method allows to perform spherical deconvolution of multiple anisotropic response functions, specifically improving the performances of spherical deconvolution in GM tissue. HighlightsO_LIWe introduce a novel framework to perform spherical deconvolution with multiple anisotropic response functions (mFOD) C_LIO_LIWe show that the proposed framework can be used to improve the FOD estimation in the cortical grey matter C_LIO_LIFiber tractography performed with mFOD reaches the cortical GM with more coverage and contiguity than with previous methods C_LIO_LIThe proposed framework is a first step towards GM to GM fiber tractography C_LI

bioinformatics↗

bioRxiv2019

Nonlinear Dispersive Cell Model for Microdosimetry of Nanosecond Pulsed Electric Fields

For nanosecond pulsed electric fields (nsPEFs) based application, the underlying transmembrane potential (TMP) distribution of the plasma membrane is influenced by electroporation (EP) of the plasma membrane and dispersion (DP) of all cell compartments and is important for predicting the bioelectric effects. In this study, we analysed temporal and spatial distribution of TMP induced by nsPEFs of various durations (3 ns, 5 ns unipolar, 5 ns bipolar, and 10 ns) with the consideration of both DP and EP. Based on the double-shelled dielectric spherical cell model, we used second-order Debye equation to characterize the dielectric relaxation of plasma membrane and nuclear membrane in the frequency domain and transformed the Debye equation into the time domain with the introduction of polarization vector, then we obtained the time course of TMP by solving the combination of Laplace equation and time-domain Debye equation. Next, we used the asymptotic version of the smoluchowski equation to characterize electroporation of plasma membrane and added it to our model to achieve the temporal and spatial distribution of TMP and pore density. Much faster and more pronounced increased in TMP can be found with the consideration of dielectric relaxation of plasma membrane and nuclear membrane, and much larger electroporated area of at least half of the plasma membrane was obtained with the consideration of both DP and EP. Through the simulation it is clearer to understand the relationship.

bioengineering↗

bioRxiv2019

Subcellular analyses of planarian meiosis implicates a novel, double-membraned vesiculation process in nuclear envelope breakdown

AO_SCPLOWBSTRACTC_SCPLOWThe cell nuclei of Ophisthokonts, the eukaryotic supergroup defined by fungi and metazoans, is remarkable in the constancy of both their double-membraned structure and protein composition. Such remarkable structural conservation underscores common and ancient evolutionary origins. Yet, the dynamics of disassembly and reassembly displayed by Ophisthokont nuclei vary extensively. Besides closed mitosis in fungi and open mitosis in some animals, little is known about the evolution of nuclear envelope break down (NEBD) during cell division. Here, we uncovered a novel form of NEBD in primary oocytes of the flatworm Schmidtea mediterranea. From zygotene to metaphase II, both nuclear envelope (NE) and peripheral endoplasmic reticulum (ER) expand notably in size, likely involving de novo membrane synthesis. 3-D electron microscopy reconstructions demonstrated that the NE transforms itself into numerous double-membraned vesicles similar in membrane architecture to NE doublets in mammalian oocytes after germinal vesicle breakdown. The vesicles are devoid of nuclear pore complexes and DNA, yet are loaded with nuclear proteins, including a planarian homologue of PIWI, a protein essential for the maintenance of stem cells in this and other organisms. Our data contribute a new model to the canonical view of NE dynamics and support that NEBD is an evolutionarily adaptable trait in multicellular organisms.

cell biology↗