Biology subjects

Hannezo, E.

Publications and source records attributed to Hannezo, E..

40 records · Page 3Linked to original sources

bioRxiv2019

DoUble resin Casting micro computed Tomography (DUCT) reveals biliary and vascular pathology in a mouse model of Alagille syndrome

BACKGROUND AND AIMSAlagille syndrome, like several other liver diseases, is characterized by malformation of lumenized structures, such as the circulatory or biliary systems. Liver architecture has typically been studied through 2D sections and, more recently, using thick tissue sections combined with immunofluorescence. We aimed to develop a robust method to image, digitalize and quantify 3D architecture of the biliary and vascular systems in tandem. METHODSThe biliary and portal vein trees of the mouse liver were injected with Microfil resin, followed by microCT scanning. Tomographic data was segmented and analyzed using a MATLAB script we wrote to investigate length, volume, tortuosity, branching, and the relation between the vascular and biliary systems. Double resin casting micro computed tomography (DUCT) was applied to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), in which the biliary system is absent at postnatal stages, but regenerates by adulthood. Phenotypes discovered using DUCT were validated with cumbersome consecutive liver sections from mouse and human liver including patients with Alagille syndrome. RESULTSDUCT revealed tortuous bile ducts either placed further from portal veins, or ectopically traversing the parenchyma and connecting two portal areas, in Jag1Ndr/Ndr mice. Furthermore, bile ducts either ended abruptly, or branched independently of portal vein branching, with bifurcations placed hilar or peripheral to portal vein branches. The branching defects, parenchymal bile ducts, and blunt endings were confirmed in patient samples. CONCLUSIONDUCT is a powerful technique, which provides computerized 3D reconstruction of casted networks. It exposes and quantifies previously unknown vascular and biliary phenotypes in mouse models, revealing new phenotypes in patients. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/848481v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1565121org.highwire.dtl.DTLVardef@1e86cfcorg.highwire.dtl.DTLVardef@4b4cc3org.highwire.dtl.DTLVardef@19cb20e_HPS_FORMAT_FIGEXP M_FIG C_FIG

pathology↗

bioRxiv2019

Abscission couples cell division to embryonic stem cell fate

Cell fate transitions are key to development and homeostasis. It is thus essential to understand the cellular mechanisms controlling fate transitions. Cell division has been implicated in fate decisions in many stem cells, including neuronal and epithelial progenitors. In other stem cells, such as embryonic stem (ES) cells, the role of division remains unclear. Here we show that exit from naive pluripotency in mouse ES cells generally occurs after a division. We further show that exit timing is strongly correlated between sister cells, which remain connected by cytoplasmic bridges long after division, and that bridge abscission progressively accelerates as cells exit naive pluripotency. Finally, interfering with abscission impairs exit from naive pluripotency. Altogether, our data indicate that a switch in the division machinery leading to faster abscission is crucial for pluripotency exit. Our study identifies abscission as a key step coupling cell division to fate transitions.

cell biology↗

bioRxiv2019

Constrained actin dynamics emerges from variable compositions of actin regulatory protein complexes

Assemblies of actin and its regulators underlie the dynamic morphology of all eukaryotic cells. To begin to understand how diverse regulatory proteins work together to generate actin-rich structures we tracked the assembly of actin regulators and their relative proportions in a cell-free system that generates filopodia-like structures (FLS). We found that heterogeneous mixtures of regulators could give rise to morphologically similar structures and that the FLS actin bundles exhibited simple dynamic behaviour of growth and shrinkage. To explain these observations, we combined experiment with theory, and found that stochastic fluctuations between redundant actin regulatory subcomplexes can account for the actin dynamics. Comparing the localizations of a variety of endogenous actin regulators in Drosophila embryos and distributions of filopodia lengths yielded similar conclusions of heterogenous actin regulatory complexes and filopodia lengths governed by a stochastic growth process. Our results explain how weakly-associating assemblies of regulatory proteins can produce robust functional outcomes.

cell biology↗

bioRxiv2018

Theory of mechano-chemical patterning in biphasic biological tissues

The formation of self-organized patterns is key to the morphogenesis of multicellular organisms, although a comprehensive theory of biological pattern formation is still lacking. Here, we propose a biologically realistic and unifying approach to emergent pattern formation. Our biphasic model of multicellular tissues incorporates turnover and transport of morphogens controlling cell differentiation and tissue mechanics in a single framework, where one tissue phase consists of a poroelastic network made of cells and the other is the extracellular fluid permeating between cells. While this model encompasses previous theories approximating tissues to inert monophasic media, such as Turings reaction-diffusion model, it overcomes some of their key limitations permitting pattern formation via any two-species biochemical kinetics thanks to mechanically induced cross-diffusion flows. Moreover, we unravel a qualitatively different advection-driven instability which allows for the formation of patterns with a single morphogen and which single mode pattern scales with tissue size. We discuss the potential relevance of these findings for tissue morphogenesis.

biophysics↗