Publications
Eman Hijaze, Tsvia Gildor, Ronald Seidel, Majed Layous, Mark Winter, Luca Bertinetti, Yael Politi, Smadar Ben-Tabou de-Leon, eLife (2024).
From eLife assessment: This valuable study addresses the role of Rho-associated coiled-coil kinase (ROCK) and the cytoskeleton in the initiation and growth of the calcified endoskeleton of sea urchin embryos. Perturbation by two independent approaches provide convincing evidence that ROCK participates both in actomyosin regulation and in the gene regulatory network that controls skeletogenesis. Exciting areas of future work will be to elucidate the mechanisms by which ROCK influences gene expression and to further dissect the role of the cytoskeleton in mineralization.
Ferdinand Marletaz, Arnaud Couloux, Julie Poulain, ..., Smadar Ben-Tabou de-Leon, ... Maria Ina Arnone, Christian Gache, Thierry Lepage, Cell Genomics (2023).
This paper is an outcome of years of sequencing and analysis of the genome of the Mediterranean sea urchin, P. lividus, by a large group of European researchers, lead by Thierry Lepage and Ferdinand Marletaz. Except from generating a high quality genome sequence that we are glad to use, the paper shows that the inter-chromosomal gene order was mixed rapidly in the evolution of sea urchin species but the overall chromosomal architecture is conserved.
Hagit Kvitt, Assaf Malik, Smadar Ben-Tabou de-Leon, Eli Shemesh, Maya Lalzar, David F. Gruber, Hanna Rosenfeld, Tuo Shi, Tali Mass and Dan Tchernov, Frontiers in Marine Science (2022)
Deoxygenation, the reduction of oxygen level in the oceans induced by global warming, is a major threat to marine life and especially to coral reefs. This paper investigates the effect of two weeks of deoxygenation on the physiology and gene expression of the coral, Stylophora pistillata. These studies show that S. pistillata can acclimate to deoxygenation and possibly survive under climate change-driven oceanic deoxygenation. Yet, this acclimation critical dependce on the coral algal symbionts, suggesting that any environmental perturbations that disrupt such symbiosis will negatively affect the ability of corals to withstand ocean oxygen depletion.
Kristina Tarsis, Tsvia Gildor, Miri Morgulis and Smadar Ben-Tabou de-Leon, Developmental Dynamics (2022).
The body, post-oral, anterolateral and midventral rods that make the sea urchin larval skeleton are made of the same calcite crystal, but the elongation of each pair of rods is regulated by rod-specific set of regulatory genes. Interestingly, this variety is not reflected in the similar sets of spicule matrix proteins that are building the rods, yet the regulation is distinct. Want to know more about the rod specific gene regulatory networks and their usage? read our paper! :-)
5. The evolution of biomineralization through the co-option of organic scaffold forming networks
Smadar Ben-Tabou de-Leon, Cells (2022)
Here I compare the gene regulatory networks (GRNs) that drive biomineralization and tubulogenesis in echinoderms and in vertebrates. The GRN that drives skeletogenesis in the sea urchin embryo shows little similarity to the GRN that drives bone formation and high resemblance to the GRN that drive vertebrates’ vascular tubulogenesis. This comparisons suggests that biomineralization in deuterostomes evolved through the phylum specific co-option of GRNs that control distinct organic scaffolds.
6. The biological regulation of sea urchin larval skeletogenesis – From genes to biomineralized tissue
Tsvia Gildor, Mark R.Winter, Majed Layous, Eman Hijaze, Smadar Ben-Tabou de-Leon, J Structural Biology (2021).
Here we describe the current understanding of the genetic, molecular and cellular processes that underlie sea urchin larval skeletogenesis. We portray the regulatory genes that define the specification of the skeletogenic cells and drive the various morphogenetic processes that occur in the skeletogenic lineage. Overall, we illustrate the novel insights on the biological regulation and evolution of biomineralization, gained from studies of the sea urchin larval skeletogenesis.
Majed Layous, Lama Khalaily, Tsvia Gildor, Smadar Ben-Tabou de-Leon, Development (2021).
Deoxygenation, the reduction of oxygen level in the oceans induced by global warming and anthropogenic disturbances, is a major threat to marine life. Acute diurnal changes in oxygen levels could be especially harmful to developing embryos that are sensitive to environmental conditions. Here we show that the tolerance to hypoxic conditions changes between different developmental stages of the sea urchin embryo, due to the structure of the gene regulatory networks (GRNs). We propose that the structure of the GRN, that includes feedback and feedforward loops, increases its resilience to changes of the initial oxygen gradients and helps the embryos tolerate transient hypoxia.
8. Calcium-vesicles perform active diffusion in the sea urchin embryo during larval biomineralization
Mark R. Winter, Miri Morgulis, Tsvia Gildor, Andrew R. Cohen, Smadar Ben-Tabou de-Leon, Plos Computational Biology (2021). Highlighted in Prelights
Biomineralizing cells concentrate the mineral in vesicles that they secret into a dedicated compartment where crystallization occurs. Here we investigate the three-dimensional (3D) vesicle dynamics in control sea urchin embryos. Our findings imply that calcium vesicles perform an active diffusion motion in all the cells of the embryo and provide an unprecedented view of calcium vesicle 3D-dynamics and illuminate possible molecular mechanisms that control vesicle dynamics and deposition.
Miri Morgulis, Mark R.Winter, LigalShternhell, TsviaGildor and SmadarBen-Tabou de-Leon, Developmental Biology (2021).
In this paper we characterized the expression and regulation by VEGF signaling of two metalloproteinases, mmpl5 and mmpl7, that are highly abundant in the sea urchin clacite spicules. We also showed that mmpl7 is necessary for normal elongation of the sea urchin skeletal rods.
Tsvia Gildor, Gregory A. Cary, Maya Lalzar, Veronica F. Hinman and Smadar Ben-Tabou de-Leon, Sci. Rep. (2019)
In this paper we studied the developmental transcriptomes of the sea star, P. miniata, in comparison to those of two sea urchin species, P. lividus and S. purpuratus. Our studies suggest that the conservation in gene expression between distant species is more due to cellular and metabolic constraints than due to developmental constraints and this is reflected in the different morphology.
11. Possible cooption of a VEGF-driven tubulogenesis program for biomineralization in echinoderms.
Miri Morgulis, Tsvia Gildor, Modi Roopin, Noa Sher, Assaf Malik, Maya Lalzar, Monica Dines, Shlomo Ben-Tabou de-Leon, Lama Khalaily, and Smadar Ben-Tabou de-Leon, PNAS (2019).
The sea urchin calcite spicules and vertebrate blood vessels are quite distinct in their function, yet both have a tubular structure and are controlled by the vascular endothelial growth factor (VEGF) pathway. Here we study the downstream program by which VEGF signaling drives sea urchin spiculogenesis and find remarkable similarities to the control of vertebrate vascularization. The similarities are observed both in the upstream gene regulatory network, in the downstream effector genes, and the cellular processes that VEGF signaling controls at the site of the calcite spicule formation. We speculate that sea urchin spiculogenesis and vertebrate vascularization diverged from a common ancestral tubulogenesis program that was uniquely coopted for biomineralization in the echinoderm phylum.
12. Comparative Studies of Gene Expression Kinetics: Methodologies and Insights on Development and Evolution.
Tsvia Gildor and Smadar Ben-Tabou de-Leon, Front. Genet. 9:339 (2018)
In this review we present recent computational approaches for comparative studies of gene expression kinetics and the novel insights they provide into the developmental constraints and plasticity that shape animal body plans.
13. Parallel embryonic transcriptional programs evolve under distinct constraints and may enable morphological conservation amidst adaptation
Assaf Malik, Tsvia Gildor, Noa Sher, Majed Layous and Smadar Ben-Tabou de-Leon, Dev. Biol. (2017).
In this paper we study conservation and change in gene expression patterns between two closely related sea urchin species in a transcriptome level. We discovered that developmental and housekeeping gene expression is dynamic and conserved but the kinetic behavior or the two sets is different. The position of the stage of highest conservation (phylotypic stage) is at mid-developmental stage for developmental genes (hourglass pattern) while the conservation of housekeeping genes keeps increasing with developmental time (funnel pattern). Thus, different gene sets seem to evolve under different constraints that result with different conservation patterns, which might allow embryos to conserve their morphology while adapting to local changes.
Tsvia Gildor, Veronica Hinman and Smadar Ben-Tabou de-Leon, Int. J. Dev. Biol. (2017).
In this paper we compare the expression dynamics of regulatory genes between two echinoderm embryos that shared a common ancestor about 500 million years ago: the sea urchin and the sea star. We find that despite the large evolutionary distance and morphological differences between the embryos there are only mild heterochronies between the expression dynamics of regulatory genes in all embryonic territories. This finding emphasize the strong developmental constraints that do not permit evolutionary change of the expression dynamics of core developmental regulatory genes over 500 million years of parallel evolution.
Tsvia Gildor, Assaf Malik, Noa Sher and Smadar Ben-Tabou de-Leon, Developmental Biology, (2016).
In this paper we discover that the maternal mRNAs are longer than zygotic mRNA in sea urchin embryos, specifically, their coding sequences and 3'UTR. We also find that the turn-over rates due to maternal and zygotic degradation mechanisms are not correlated.
16. Robustness and accuracy in sea urchin developmental gene regulatory networks
Smadar Ben-Tabou de-Leon, Frontiers in genetics, (2016).
In this perspective I propose that the use of specific architectures by the sea urchin developmental regulatory networks enables the robust control of cell fate decisions.
17. Quantitative Developmental Transcriptomes of the Mediterranean sea urchin, Paracentrotus lividus
Tsvia Gildor, Assaf Malik, Noa Sher, Linor Avraham and Smadar Ben-Tabou de-Leon, Marine Genomics, 25, 89-94, (2016).
In this paper we study the developmental transcriptomes of P. lividus at seven developmental time points, from the fertilized egg to the prism stage. This study portrays the rich patterns of temporal genes expression that drive sea urchin embryogenesis and provide and essential recourse for the sea urchin community.
Tsvia Gildor, and Smadar Ben-Tabou de-Leon, Plos Genetics (2015).
In this paper we detect striking interspecies conservation of the expression dynamics of regulatory and differentiation genes between two sea urchin species that are geographically and genetically distant. This study demonstrates the amazing ability of gene regulatory networks to conserve expression dynamics over 50 million years of evolution.