Biology subjects

Özbek, S.

Publications and source records attributed to Özbek, S..

3 recordsLinked to original sources

bioRxiv2024

Molecular dynamics of the matrisome across sea anemone life history

The evolutionary expansion of extracellular matrix (ECM) molecules has been crucial for the establishment of cell adhesion and the transition from unicellular to multicellular life. Members of the early diverging metazoan phylum cnidaria offer an exceptionally rich perspective into the metazoan core adhesome and its original function in developmental and morphogenetic processes. Here, we present the ensemble of ECM proteins and associated factors for the starlet sea anemone Nematostella vectensis based on in silico prediction and quantitative proteomic analysis of decellularized mesoglea from different life stages. The integration of the matrisome with single cell transcriptome atlases shows that gastrodermal cells are the primary producers of Nematostellas complex ECM, confirming the homology of the cnidarian inner cell layer with bilaterian mesoderm. The transition from larva to polyp is marked by an upregulation of metalloproteases and basement membrane components including all members of an unusually diversified SVEP1/Polydom family, suggesting massive epithelial remodeling. The enrichment of Wnt/PCP pathway factors during this process further indicates directed cell rearrangements as a key contributor to the polyps morphogenesis. Mesoglea maturation in adult polyps involves wound response proteins indicating shared molecular patterns in growth and regeneration. Our study identifies conserved matrisomal networks that coordinate transitions in Nematostellas life history.

developmental biology↗

bioRxiv2021

How Dickkopf molecules and Wnt/beta-catenin interplay to self-organise the Hydra body axis

The antagonistic interplay between canonical Wnt signalling and Dickkopf (Dkk) proteins is fundamental to tissue organisation, including stem cell differentiation and body-axis formation. Disruptions in this interaction are linked to various human diseases, yet the mechanisms enabling robust body-axis formation through {beta}-catenin/Wnt-Dkk interactions remain unclear. A key model system for Wnt-driven pattern formation is the pre-bilaterian organism Hydra, where two ancestral Dkk proteins interact with Wnt signalling to self-organise the body axis. While Hydra patterning has been extensively studied using the activator-inhibitor framework, a model integrating experimentally identified molecules has been lacking. Here, we introduce a mathematical model that incorporates both Dkks and their experimentally observed interactions with Wnt signalling. Numerical and analytical studies show that this network alone is sufficient to drive de novo body-axis formation across a broad parameter range. Our mutual inhibition model provides a biologically grounded realization of the general local-activation/long-range-inhibition (LALI) principle of de novo pattern formation, offering a mechanistic explanation for the observed Dkk and Wnt expression patterns under various conditions. Unlike previous models, it is directly grounded in experimental data, links injury response to pattern formation, and remains robust against perturbations. Author SummaryHow organisms form and regenerate complex body structures is a fundamental question in biology. In the freshwater animal Hydra, which can regenerate its entire body from a small tissue fragment, a molecular signalling system involving Wnt proteins and their inhibitors, the Dickkopf (Dkk) family, plays a central role in organising the body axis. While these molecules are known to interact, their exact roles and how they collectively shape large-scale patterns have remained unclear--especially since their activity does not fully align with established pattern formation models. In this study, we present a new mathematical model that captures the observed interactions between Wnt and two Dkk molecules in Hydra. We show that a mechanism based on mutual inhibition--rather than the traditional interplay between activator and inhibitor molecules--can explain the emergence of a stable body axis and the results of various perturbation experiments. Our work offers new insights into the design principles of biological pattern formation and emphasizes the importance of exploring alternative mechanisms beyond classical theories.

developmental biology↗

bioRxiv2017

Spatio-temporal elasticity patterns in extracellular matrix during Hydra morphogenesis

Albeit ample evidence has suggested the remodeling of extracellular matrix (ECM) in animals plays crucial roles in development and diseases, little is understood how ECM mechanics correlates with tissue morphogenesis. In this study, we quantitatively determined how spatio-temporal elasticity patterns in ECM change during the asexual reproduction of freshwater polyp Hydra. We first determined the mesoscopic protein arrangement in Hydra ECM (mesoglea) by grazing-incidence small-angle X-ray scattering with nano-beam (nano-GISAXS). Our data unraveled fibrillar type I collagen in Hydra mesoglea (Hcol-I) takes an anisotropic, more strongly distorted hexagonal lattice compared to those in vertebrates that could be attributed to the lower proline content and lack of lysin-crosslinks in Hcol-1 fibers. Then, we "mapped" the spatio-temporal changes in ECM stiffness ex vivo with aid of nano-indentation. We identified three representative elasticity patterns during tissue growth along the oral-aboral body axis of the animals. Our complementary proteome analysis demonstrated that the elasticity patterns of the ECM correlate with a gradient like distribution of proteases. Perturbations of the oral Wnt/{beta}-catenin signaling center further indicated that ECM elasticity patterns are governed by Wnt/{beta}-catenin signaling. The ex vivo biomechanical phenotyping of Hydra mesoglea established in this study will help us gain comprehensive insights into the spatio-temporal coordination of biochemical and biomechanical cues in tissue morphogenesis in vivo.

developmental biology↗