Biology subjects

Simon, C. S.

Publications and source records attributed to Simon, C. S..

10 recordsLinked to original sources

bioRxiv2026

Septin-mediated coupling of protein import and division during chloroplast evolution

Chloroplast biogenesis depends on both protein import and organelle division, yet how their coordination emerged during evolution remains unclear. Here, we show that the single septin SEP1 links these pathways in the green alga Chlamydomonas reinhardtii. SEP1 forms a filamentous network on the chloroplast envelope during interphase and reorganizes into a ring at the chloroplast division site during cytokinesis. Loss of SEP1 selectively impairs import of chloroplast-division proteins and causes mispositioning of the division ring, without impairing bulk chloroplast protein import. SEP1 physically associates with outer-envelope TOC GTPases through evolutionarily related GTPase domains. Phylogenetic analysis places TOC GTPases within an algal septin-derived clade, and heterologous expression of SEP1 in land plants, in which septins are absent, shows conservation of its chloroplast targeting and TOC binding. Together, these findings identify septins as coordinators of plastid protein import and division and suggest that this coupling emerged early in chloroplast evolution.

cell biology↗

bioRxiv2026

Basement membrane mechanics drives patterned response to developmental signalling

Precise spatiotemporal patterning of cell fate decisions during development, such as those accompanying gastrulation, has traditionally been attributed to morphogen gradients. Emerging evidence also points to a crucial role for mechanics in regulating cell fate decisions. Here, we uncover that basement membrane mechanics in human pluripotent stem cells (hPSCs) regulates the spatiotemporal response to gastrulation-inducing BMP4. Reducing mechanosensation via soft substrates or chemical inhibitors abolishes stereotypical spatial patterning of the BMP4 response in hPSC colonies. This loss arises from disrupted epithelial polarity and increased permeability, which enhance BMP receptor accessibility. Strikingly, apical exposure to soluble laminin similarly disrupts polarity and suppresses hPSC mechanosensing, phenocopying the soft substrates effect and suggesting feedback between polarity signaling and mechanosensing. Finally, softening the basement membrane in mouse embryos triggers ectopic and premature mesoderm differentiation, disrupting gastrulation patterning. Together, this study describes a mechanochemical feedback mechanism that establishes basement membrane mechanics as a key regulator of developmental patterning.

cell biology↗

bioRxiv2025

Changes in the health-related ecosystem services and disservices provided by urban trees over multiple decades in a small city

The effects of urban trees on public health should change over decades due to shifts in tree composition and abundance, environmental conditions, human demography, and disease incidence. However, there are few case studies documenting changes in the health-related ecosystem services and disservices provided by trees over time. Here we use seven tree censuses to quantify changes in the effects of city-owned trees on air pollution, allergenic pollen, hydrology, and heat due to shifts in tree abundance and environmental conditions in Ithaca, New York, a small city in the Northeastern United States. We also review how shifts in disease incidence have affected these trees health consequences. From 2005 to 2021, trees removed 20% more ozone and 268% more PM2.5; they also removed substantially more runoff and had higher cooling capacity. In contrast, the amount of certain air pollutants removed by trees dropped from 2005 to 2021 for sulfur dioxide (361 kg/yr to 8 kg/yr), carbon monoxide (65 kg/yr to 32 kg/yr), and nitrogen dioxide (380 kg/yr to 298 kg/yr) as their ambient concentrations dropped. Pollen production by street trees from 1947 to 2021 initially dropped due to Dutch elm disease but has quadrupled since the 1980s due to increases in several high-pollen producing genera. Overall, this study illustrates how the public health effects of trees vary over decades due to changes in tree composition and abundance, environmental conditions, and changes in disease incidence and human demography, emphasizing the importance of incorporating long-term perspectives into contemporary tree management decisions. Highlights[bullet] Urban trees health-related ecosystem services changed over decades in a case study [bullet]The removal of SO2, NO2, and CO by urban trees is diminishing due to cleaner air [bullet]Shifts in tree composition have had large effects on allergenic pollen production [bullet]Changes in human disease incidence over decades mediate trees health effects

ecology↗

bioRxiv2024

ETV4 and ETV5 Orchestrate FGF-Mediated Lineage Specification and Epiblast Maturation during Early Mouse Development

Cell fate decisions in early mammalian embryos are tightly regulated processes crucial for proper development. While FGF signaling plays key roles in early embryo patterning, its downstream effectors remain poorly understood. Our study demonstrates that the transcription factors Etv4 and Etv5 are critical mediators of FGF signaling in cell lineage specification and maturation in mouse embryos. We show that loss of Etv5 compromises primitive endoderm formation at pre-implantation stages. Furthermore, Etv4/5 deficiency delays naive pluripotency exit and epiblast maturation, leading to elevated NANOG and reduced OTX2 expression within the blastocyst epiblast. As a consequence of delayed pluripotency progression, Etv4/5 deficient embryos exhibit anterior visceral endoderm migration defects post-implantation, a process essential for coordinated embryonic patterning and gastrulation initiation. Our results demonstrate the successive roles of these FGF signaling effectors in early lineage specification and embryonic body plan establishment, providing new insights into the molecular control of mammalian development. Summary statementFGF signaling effectors ETV4/5 regulate lineage specification and embryo patterning in mice, affecting primitive endoderm formation and pluripotency exit.

developmental biology↗

bioRxiv2024

Suppression of ERK signalling promotes pluripotent epiblast in the human blastocyst

Studies in the mouse demonstrate the importance of fibroblast growth factor (FGF) and extra-cellular receptor tyrosine kinase (ERK) in specification of embryo-fated epiblast and yolk-sac-fated hypoblast cells from uncommitted inner cell mass (ICM) cells prior to implantation. Molecular mechanisms regulating specification of early lineages in human development are comparatively unclear. Here we show that exogenous FGF stimulation leads to expanded hypoblast molecular marker expression, at the expense of the epiblast. Conversely, we show that specifically inhibiting ERK activity leads to expansion of epiblast cells functionally capable of giving rise to naive human pluripotent stem cells. Single-cell transcriptomic analysis indicates that these epiblast cells downregulate FGF signalling and upregulate molecular markers associated with naive pluripotency. Our functional study demonstrates for the first time the molecular mechanisms governing ICM specification in human development, whereby segregation of the epiblast and hypoblast lineages occurs during maturation of the mammalian embryo in an ERK signal-dependent manner.

developmental biology↗

bioRxiv2022

An Sfi1-like centrin-interacting centriolar plaque protein affects nuclear microtubule homeostasis.

Malaria-causing parasites achieve rapid proliferation in human blood through multiple rounds of asynchronous nuclear division followed by daughter cell formation. Nuclear divisions critically depend on the centriolar plaque, which organizes intranuclear spindle microtubules. The centriolar plaque consists of an extranuclear compartment, which is connected via a nuclear pore-like structure to a chromatin-free intranuclear compartment. Composition and function of this non-canonical centrosome remain largely elusive. Centrins, which reside in the extranuclear part, are among the very few centrosomal proteins conserved in Plasmodium falciparum. Here we identify a novel centrin-interacting centriolar plaque protein. Conditional knock down of this Sfi1-like protein (PfSlp) caused a growth delay in blood stages, which correlated with a reduced number of daughter cells. Surprisingly, intranuclear tubulin abundance was significantly increased, which raises the hypothesis that the centriolar plaque might be implicated in regulating tubulin levels. Disruption of microtubule homeostasis caused polymerization of excess microtubules and aberrant mitotic spindles. Time-lapse microscopy revealed that this prevented or delayed spindle extension. Our study thereby identifies a novel extranuclear centriolar plaque factor and establishes a functional link to the intranuclear compartment of this divergent eukaryotic centrosome.

cell biology↗

bioRxiv2022

A conserved role of Hippo signaling in initiation of the first lineage specification event across mammals

Our understanding of the molecular events driving cell specification in early mammalian development relies mainly on mouse studies, and it remains unclear whether these mechanisms are conserved across mammals, including humans. We have recently shown that the establishment of cell polarity via aPKC is a conserved event in the initiation of the trophectoderm (TE) placental program in mouse, cow, and human embryos. However, the molecular mechanisms transducing cell polarity into cell fate in cow and human embryos is unknown. Here, we have examined the evolutionary conservation of the molecular cascade downstream of aPKC in four different mammalian species: mouse, rat, cow, and human. Surprisingly, by morphokinetic and immunofluorescence analyses, we observe that rat embryos more closely recapitulate human and cow developmental dynamics, in comparison to the mouse. Nevertheless, in all four species, inhibition of the Hippo pathway by targeting LATS kinases is sufficient to drive ectopic TE initiation and downregulation of SOX2, a marker of the inner cell mass. Our comparative embryology approach uncovered intriguing differences as well as similarities in a fundamental developmental process among mammals, reinforcing the importance of cross-species investigations.

developmental biology↗

bioRxiv2021

An extended DNA-free intranuclear compartment organizes centrosomal microtubules in Plasmodium falciparum

Rapid proliferation of Plasmodium falciparum parasites in human red blood cells is the cause of malaria and is underpinned by an unconventional cell division mode, called schizogony. Contrary to model organisms, P. falciparum replicates by multiple rounds of closed and asynchronous nuclear divisions that are not interrupted by cytokinesis. Organization and dynamics of the critical nuclear division factors are, however, poorly understood. Centriolar plaques, the centrosomes of P. falciparum, are important regulators of division and serve as microtubule organizing centers. Early microscopy studies reveal an acentriolar, amorphous structure although its detailed organization remains elusive. Intranuclear microtubules mediate chromosome segregation, but the small size of parasite nuclei has precluded detailed analysis of their arrangement by classical fluorescence microscopy. We apply recently developed STED, expansion microscopy, and live cell imaging protocols to describe the reconfiguration of microtubules during schizogony. Analysis of centrin, nuclear pore, and microtubule positioning reveals a bipartite organization of the centriolar plaque. While centrin is extranuclear, we confirm by correlative light and electron tomography that microtubules are nucleated in a previously unknown and extended intranuclear compartment, which is devoid of chromatin. This study enables us to build a working model of the organization of an unconventional centrosome and better understand the diversity of eukaryotic cell division modes.

cell biology↗

bioRxiv2021

Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence

The pathology associated with malaria infection is largely due to the ability of infected human erythrocytes to adhere to a number of receptors on endothelial cells within tissues and organs. This phenomenon is driven by the export of parasite-encoded proteins to the host cell, the exact function of many of which is still unknown. Here we inactivate the function of one of these exported proteins, PFA66, a member of the J-domain protein family. Although parasites lacking this protein were still able to grow in cell culture, we observed severe defects in normal host cell modification, including aberrant morphology of surface knobs, disrupted presentation of the cytoadherence molecule PfEMP1, and a total lack of cytoadherence, despite the presence of the knob associated protein KAHRP. Complementation assays demonstrate that an intact J-domain is required for recovery to a wild-type phenotype and suggest that PFA66 functions in concert with a HSP70 to carry out host cell modification. Strikingly, this HSP70 is likely to be of host origin. Taken together, our data reveal a role for PFA66 in host cell modification, implicate human HSP70 as also being essential in this process, and uncover a KAHRP-independent mechanism for correct knob biogenesis. Our observations open up exciting new avenues for the development of new anti-malarials.

cell biology↗

bioRxiv2018

Charting the emergent organotypic landscape of the mammalian gut endoderm at single-cell resolution

To comprehensively delineate the ontogeny of an organ system, we generated 112,217 singlecell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. We employed graph-based approaches to model differentiating cells for spatio-temporal characterization of developmental trajectories. Our analysis reveals the detailed architecture of the emergence of the first (primitive or extra-embryonic) endodermal population and pluripotent epiblast. We uncover an unappreciated relationship between descendants of these lineages, before the onset of gastrulation, suggesting that mixing of extra-embryonic and embryonic endoderm cells occurs more than once during mammalian development. We map the trajectories of endoderm cells as they acquire embryonic versus extra-embryonic fates, and their spatial convergence within the gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observe the regionalized localization of cells along the forming gut tube, reflecting their extra-embryonic or embryonic origin, and their coordinate patterning into organ-specific territories along the anterior-posterior axis.

developmental biology↗