Biology subjects

Wilsch-Braeuninger, M.

Publications and source records attributed to Wilsch-Braeuninger, M..

4 recordsLinked to original sources

bioRxiv2025

Species-specific basal fluidization shapes early forebrain development

The human forebrain exhibits an expanded surface area compared with other great apes. Despite progress in dissecting species-specific gene expression programs and cell lineages, the tissue-level physical mechanisms underlying human-specific neurodevelopment remain unclear. Here, by quantifying tissue dynamics and mechanics using oil microdroplets in cerebral organoids from humans, gorillas, chimpanzees, and mice, we uncover a transient tissue fluidization occurring exclusively in the basal region of human neuroepithelia. Enhanced droplet motility and frequent cell rearrangements reveal this basal fluidization, which gradually diminishes at the onset of neurogenesis in humans. By contrast, such basal fluidization is not detected in non-human neuroepithelia examined here. Mechanistically, basal fluidization is driven by basal nuclear fluctuations and facilitated by expanded intercellular spaces. Increasing N-cadherin expression in human neuroepithelia to gorilla levels suppresses both nuclear fluctuations and basal fluidization. Integrating simulations of neuroepithelial dynamics with experimental data, we further find that nuclear fluctuations underlying basal fluidization promote the insertion of newly divided nuclei into the basal side to support tangential surface expansion, a hallmark of human forebrain development.

developmental biology↗

bioRxiv2024

The Role of Purine Interactions in Biogenic Crystal Shape Determination

Widespread through phyla, purine crystals are intracellular inclusions serving a myriad of organismal functions. In zebrafish, iridophores concentrate purines in membrane-bound organelles, the iridosomes, for controlled crystallization. These crystals assemble into large, flat, and thin hexagons following unknown mechanisms that evolve against thermodynamically favorable interactions. Here, we investigate the initial development of zebrafish iridosomal crystals. By performing in vivo confocal reflection imaging, cryoFIB-SEM, and establishing novel 2D and 3D analysis pipelines, we show that these crystals grow four times faster along the b-crystallographic axis, leading to their characteristic hexagonal shape. By analyzing zebrafish with impaired guanine production, while conducting crystal growth simulations, we find that crystal shape is directed by bond type, number, and interaction strength between purines. Mechanistically, the macroscopic shape of zebrafish crystals is controlled by the relative concentration of purines present in the iridosome. This process impacts crystal growth along the b-axis, by disrupting the crystals in-plane hydrogen bond structure, without alteration of the other axes. Our work uncovers a layer of biogenic crystal growth regulation occurring in vertebrate biocrystallization processes. HighlightsO_LIZebrafish iridophores actively regulate crystal size and shape within iridosomes C_LIO_LIIn vivo crystal (100) facet grows [~]4m{superscript 2} in 24 hours C_LIO_LILength of crystallographic b-axis is controlled by purine molecular interactions C_LIO_LISize of c- and a-axes is regulated independently of b-axis C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=180 SRC="FIGDIR/small/613275v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@1946819org.highwire.dtl.DTLVardef@3e6d34org.highwire.dtl.DTLVardef@737212org.highwire.dtl.DTLVardef@1462501_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2022

Cerebral organoids expressing mutant actin genes reveal cellular mechanism underlying microcephalic cortical malformation

Actins are structural cytoskeletal proteins playing crucial roles in multiple cellular processes. Mutations in the ACTB and ACTG1 genes, encoding the ubiquitous beta- and gamma- cytoskeletal actin isoforms, respectively, cause a broad spectrum of neurodevelopmental disorders, with microcephaly as the most frequent one. Here we used patient-derived cerebral organoids to gain insight into the pathogenesis underlying this cortical malformation. Cerebral organoids from induced pluripotent stem cells (iPSCs) of patients with the Baraitser-Winter- CerebroFrontoFacial syndrome (BWCFF-S), expressing either an ACTB or an ACTG1 missense mutation, are reduced in size, showing a thinner ventricular zone (VZ). This decrease in VZ progenitors is in turn associated with a striking change in the orientation of their cleavage plane from predominantly vertical (control) to predominantly horizontal (BWCFF-S), which is incompatible with increasing VZ progenitor abundance. Various cytoskeletal and morphological irregularities of BWCFF-S VZ progenitors, notably in the apical region of these cells, seemingly contribute to their predominantly horizontal cleavage plane orientation. Our results provide insight into the cell biological basis of the microcephaly associated with BWCFF-S caused by actin mutations.

neuroscience↗

bioRxiv2019

Metabolic control of YAP via the acto-myosin system during liver regeneration

The mechanisms of organ size control remain poorly understood. A key question is how cells collectively sense the overall status of a tissue. We addressed this problem focusing on mouse liver regeneration, which is controlled by Hippo signalling. Using digital tissue reconstruction and quantitative image analysis, we found that the apical surface of hepatocytes forming the bile canalicular network expands concomitant with an increase of F-actin and phospho-Myosin, to compensate an overload of bile acids. Interestingly, these changes are sensed by the Hippo transcriptional co-activator YAP, which localizes to the apical F-actin-rich region and translocates to the nucleus in dependence of the acto-myosin system. This mechanism tolerates moderate bile acid fluctuations under tissue homeostasis, but activates YAP in response to sustained bile acid overload. Using an integrated biophysical-biochemical model of bile pressure and Hippo signalling, we explained this behaviour by the existence of a mechano-sensory mechanism that activates YAP in a switch-like manner. We propose that the apical surface of hepatocytes acts as a self-regulatory mechano-sensory system that responds to critical levels of bile acids as readout of tissue status.

systems biology↗