Organisme multicellulaire | EPFL Graph Search

Un organisme multicellulaire (ou pluricellulaire) est un organisme vivant composé de plusieurs cellules, différenciées ou non, en contact. Les organismes qui peuvent être vus à l'œil nu sont habituellement multicellulaires, mais certains organismes unicellulaires, notamment des myxomycètes, sont également visibles sans utiliser de microscope. Un groupe de cellules semblables qui assurent une fonction au sein d'un organisme multicellulaire est appelé tissu. Histoire évolutive Jusqu'en 2010, le plus ancien organisme multicellulaire connu était une algue rouge appelée Bangiomorpha pubescens ; elle a été trouvée fossilisée dans des roches de la période géologique de l'Ectasien datant de 1,2 milliard d'années, dans l'ère Mésoprotérozoïque. Toutefois, un groupe fossile d'organismes multicellulaires a été découvert en 2010 dans des sédiments gabonais, repoussant l'apparition des premiers organismes multicellulaires à plus de 2,1 milliards d'années ; en 2014, le CNRS a définit

Integrin-Mediated Adhesion in the Unicellular Holozoan Capsaspora owczarzaki

Omaya Pierre Dudin

In animals, cell-matrix adhesions are essential for cell migration, tissue organization, and differentiation, which have central roles in embryonic development [1-6]. Integrins are the major cell surface adhesion receptors mediating cell-matrix adhesion in animals. They are heterodimeric transmembrane proteins that bind extracellular matrix (ECM) molecules on one side and connect to the actin cytoskeleton on the other [7]. Given the importance of integrin-mediated cell-matrix adhesion in development of multicellular animals, it is of interest to discover when and how this machinery arose during evolution. Comparative genomic analyses have shown that core components of the integrin adhesome pre-date the emergence of animals [8-11]; however, whether it mediates cell adhesion in non-metazoan taxa remains unknown. Here, we investigate cell-substrate adhesion in Capsaspora owczarzaki, the closest unicellular relative of animals with the most complete integrin adhesome [11, 12]. Previous work described that the life cycle of C. owczarzaki (hereafter, Capsaspora) includes three distinct life stages: adherent; cystic; and aggregative [13]. Using an adhesion assay, we show that, during the adherent life stage, C. owczarzaki adheres to surfaces using actin-dependent filopodia. We show that integrin b2 and its associated protein vinculin localize as distinct patches in the filopodia. We also demonstrate that substrate adhesion and integrin localization are enhanced by mammalian fibronectin. Finally, using a specific antibody for integrin b2, we inhibited cell adhesion to a fibronectin-coated surface. Our results suggest that adhesion to the substrate in C. owczarzaki is mediated by integrins. Wethus propose that integrin-mediated adhesion pre-dates the emergence of animals.

CELL PRESS2020

Regulation of sedimentation rate shapes the evolution of multicellularity in a close unicellular relative of animals

Omaya Pierre Dudin

Significant increases in sedimentation rate accompany the evolution of multicellularity. These increases should lead to rapid changes in ecological distribution, thereby affecting the costs and benefits of multicellularity and its likelihood to evolve. However, how genetic and cellular traits control this process, their likelihood of emergence over evolutionary timescales, and the variation in these traits as multicellularity evolves are still poorly understood. Here, using isolates of the ichthyosporean genus Sphaeroforma-close unicellular relatives of animals with brief transient multicellular life stages-we demonstrate that sedimentation rate is a highly variable and evolvable trait affected by at least 2 distinct physical mechanisms. First, we find extensive (>300x) variation in sedimentation rates for different Sphaeroforma species, mainly driven by size and density during the unicellular-to-multicellular life cycle transition. Second, using experimental evolution with sedimentation rate as a focal trait, we readily obtained, for the first time, fast settling and multicellular Sphaeroforma arctica isolates. Quantitative microscopy showed that increased sedimentation rates most often arose by incomplete cellular separation after cell division, leading to clonal "clumping" multicellular variants with increased size and density. Strikingly, density increases also arose by an acceleration of the nuclear doubling time relative to cell size. Similar size- and density-affecting phenotypes were observed in 4 additional species from the Sphaeroforma genus, suggesting that variation in these traits might be widespread in the marine habitat. By resequencing evolved isolates to high genomic coverage, we identified mutations in regulators of cytokinesis, plasma membrane remodeling, and chromatin condensation that may contribute to both clump formation and the increase in the nuclear number-to-volume ratio. Taken together, this study illustrates how extensive cellular control of density and size drive sedimentation rate variation, likely shaping the onset and further evolution of multicellularity.

PUBLIC LIBRARY SCIENCE2022

Microfluidic iMITOMI platform to study the architecture of low-affinity transcription factor binding site clusters

Ivan Istomin

Gene regulatory networks (GRNs) determine cellular behaviour, and ultimately the functioning of single- and multicellular organisms. Transcription factors regulate gene expression by binding to DNA or via remodelling chromatin. Recent advances in biotechnological methods have made it possible to precisely characterise the binding of transcription factors to single consensus binding sites. Advanced sequencing methods allow the efficient discovery of de novo binding consensus sequences, and thus provide insight into the evolution of GRNs. However, clusters of transcription factor binding sites have been poorly studied despite their prevalence in eukaryotic genomes. Widely-used methods of GRN interrogation lack the sensitivity for transient binding events with low-affinity binding sites. In my PhD, using the MITOMI platform I showed that two orthologs of the transcription factor Pho4 from S. cerevisiae and C. glabrata that have evolved distinct regulation have similar 3D structure and DNA binding preferences over a wide affinity range. I have developed the iMITOMI assay that preserves the unique advantages of the original MITOMI platform, and thus too has the ability to rapidly characterise transient binding events with high-throughput. In addition, iMITOMI enables the study of transcription factor binding site clusters. We have studied in detail the interactions of Pho4 and Zif268 with clusters of one to six binding sites. The individual binding sites had affinities one to two orders of magnitude below the affinity of the corresponding consensus sequence. We discovered that clusters of low-affinity binding sites could give rise to transcription factor occupancies comparable to or higher than those of single-consensus sequences. Our results demonstrate that low-affinity binding site clusters give rise to high occupancy levels. These have significant implications for the biophysical characterisation of transcription factor binding, the de novo evolution of enhancers and promoters, and the development of synthetic promoters.

EPFL2020

Regulation of sedimentation rate shapes the evolution of multicellularity in a close unicellular relative of animals

Omaya Pierre Dudin

PUBLIC LIBRARY SCIENCE2022

Microfluidic iMITOMI platform to study the architecture of low-affinity transcription factor binding site clusters

Ivan Istomin

EPFL2020