Gene Regulation in Development and Evolution

Head of the Lab: Dr. Smadar Ben Tabou deLeon


About

 Lab overview

We aim to decipher how the genomic program for development is encoded in the DNA, how it is executed during development and what enables it to resist genetic and environmental changes. We study sea urchin and other echinoderm species that have major experimental advantages that enable us to investigate the regulation of developmental process starting from fertilization. Our research has strong implications to the understanding of cell fate specification and differentiation as well as dedifferentiation processes that occur during genetic diseases, like cancer.

overviwMajor projects in the lab where we are currently recruiting students are:

  • Vascular Endothelial Growth Factor (VEGF) pathway and sea urchin larval skeletogenesis as a model for human angiogenesis: During angiogenesis, a tumor secrets VEGF ligand to induces the growth of new blood vessels toward the tumor, enabling the tumor to grow and metastasize. In new experiments from our lab we showed that human VEGF is capable of generating ectopic skeleton in the sea urchin and that VEGF targets in the sea urchin are similar to those it activates during angiogenesis. We are now studying the molecular pathways activated by VEGF during sea urchin skeletogenesis to provide better understanding of this pathway and open the way to new therapeutic approaches. This research involves advanced quantitative methods of molecular biology and imaging. sea urchin larval skeletogenesis
  • Comparative studies of transcriptional programs between echinoderm species: The differences between the developmental transcriptional programs of different organisms underlie their different morphologies. We are studying the relation between the expression patterns of different echinoderm species and their different morphologies, to understand the evolutionary changes that underlie the emergence of new species.

Comparative studies of transcriptional programs between echinoderm specie

Fresh from our lab

2017

  • 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. In press. 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. Divergence is observed in 35% of the genes probably due to drift, but also adaptation to local environmental conditions. 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. http://www.sciencedirect.com/science/article/pii/S0012160617303421
  • Regulatory heterochronies and loose temporal scaling between sea star and sea urchin regulatory circuits, Tsvia Gildor, Veronica Hinman and Smadar Ben-Tabou de-Leon, Int. J. Dev. Biol.,2017;61(3-4-5):347-356. doi: 10.1387/ijdb.160331sb. 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. http://www.ijdb.ehu.es/web/paper/160331sb/regulatory-heterochronies-and-loose-temporal-scaling-between-sea-star-and-sea-urchin-regulatory-circuits

2016

  • Mature maternal mRNAs are longer than zygotic ones and have complex degradation kinetics in sea urchin, Tsvia Gildor, Assaf Malik, Noa Sher and Smadar Ben-Tabou de-Leon, Developmental Biology, 2016 press. 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. This indicates differential gene usage and regulation of the maternal transcripts. We also measure the turn-over rates of maternal mRNAs due to maternal and zygotic degradation mechanisms and learn that they are not correlated. This indicates that the maternal and zygotic degradation mechanisms are independent and probably relay on different regulatory seuqences in the 3'UTRs of the maternal transcripts.   http://www.sciencedirect.com/science/article/pii/S0012160615303857
  • 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. http://journal.frontiersin.org/article/10.3389/fgene.2016.00016/full
  • 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. http://www.sciencedirect.com/science/article/pii/S1874778715300556

2015

  • Comparative Study of Regulatory Circuits in Two Sea Urchin Species Reveals Tight Control of Timing and High Conservation of Expression Dynamics. 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. http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005435

Join us

We are recruiting M.Sc. and Ph.D. students. If you are interested please send your CV and research interests to:  This email address is being protected from spambots. You need JavaScript enabled to view it.

For further review of our current research projects please see Research below.
For a review of the major results of our previous work, please see Publication.
 
 

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