Biology subjects

Stuckenholz, C.

Publications and source records attributed to Stuckenholz, C..

5 recordsLinked to original sources

bioRxiv2025

Shape, Strain, and Stability: Epithelia Under High Strain

Mechanical forces play crucial roles in epithelia tissue morphogenesis and function, yet individual cells often respond differently to the same external force. Strain heterogeneity, the non-uniform deformation of cells under uniform external mechanical stimuli, may underlie tissue-level robustness and guide morphogenetic outcomes. In this study, we applied a defined uniaxial strain to Xenopus laevis epithelial explants and investigated how strain was distributed at the cellular level. Live imaging and quantitative analysis revealed that despite a uniform tissue-level strain, cellular strain was heterogeneous, suggesting variable responses to a uniform mechanical stimulus. To understand the source of this variability, we used an image analysis pipeline to explore multiple aspects of cell morphology. We found that cell intrinsic material properties, represented by Poisson index, had the strongest correlation with strain heterogeneity, suggesting a dominant role in variable mechanical response. We further analyzed how force was distributed at the cellular level using a vinculin force sensor and laser ablation. These experiments demonstrated that forces are primarily transmitted through the medio-apical actomyosin cortex whereas junctional actomyosin facilitates dissipation and remodeling. These findings provide new insights into the physical principles that underlie epithelial resilience and adaptive remodeling, highlighting the importance of distinct functions of junctional and medio-apical actomyosin networks in mechanical adaptation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/687918v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1d27474org.highwire.dtl.DTLVardef@1db811forg.highwire.dtl.DTLVardef@1fa36dforg.highwire.dtl.DTLVardef@288107_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2025

Supracellular contractility in Xenopus laevis embryonic epithelia regulated by extracellular nucleotides and the purinergic G-protein coupled receptor P2Y2.

Extracellular signals regulate epithelial homeostasis, cell fate and pattern cell behaviors during embryogenesis, wound healing, regeneration, and disease progression. Previous studies in our group found cell lysate from intentionally wounded embryos triggers a strong but transient contraction in neighboring epithelia, whether contiguous to the wound site or in non-wounded embryos. We previously identified extracellular ATP (eATP) as a possible candidate. Here we test additional candidates and find several nucleotides including ADP, UTP, and UDP also trigger contractility. Through a temporal and spatial screen of lysate activity, an inhibitor screen, and morpholino knock-down of candidate receptors, we find contractility is mediated by a G-protein coupled purinergic receptor P2Y2 (P2RY2). Activated P2RY2 triggers F-actin assembly and myosin II contractility. Knockdown of P2RY2 or overexpression of mutant G-protein effectors abrogate epithelial contractility when epithelia are exposed to eATP or lysate. We demonstrate that the major contributors to epithelial contractility in lysate are extracellular nucleotide triphosphates ATP and UTP, which are sensed by P2RY2 and transduced through G-proteins to contract the epithelium. Summary StatementContractility of the Xenopus embryonic epithelium can be driven by extracellular nucleotides ATP or UTP and actuated by the G-protein coupled purinergic receptor P2Y2 (P2RY2). HighlightsO_LIExtracellular nucleotides ATP and UTP can trigger epithelial contractility. C_LIO_LIEpithelia contract in response to (ATP [~] UTP) > (ADP [~] UDP) > ADO (adenosine). C_LIO_LIThe purinergic G-protein coupled receptor P2Y2 is responsible for this contractile response by indirectly modulating actomyosin contractility. C_LI

cell biology↗

bioRxiv2020

Furry is required for cell movements during gastrulation and functionally interacts with NDR1

Gastrulation is a key event in animal embryogenesis during which the germ layers precursors are rearranged and the embryonic axes are established. Cell polarization is essential during gastrulation driving asymmetric cell division, cell movements and cell shape changes. Furry (Fry) gene encodes an evolutionarily conserved protein with a wide variety of cellular functions mostly related to cell polarization and morphogenesis in invertebrates. However, little is known about its function in vertebrate development. Here we show that in Xenopus, Fry participates in the regulation of morphogenetic processes during gastrulation. Using morpholino knock-down, we demonstrate a role of Fry in blastopore closure and dorsal axis elongation. Loss of Fry function drastically affects the movement and morphological polarization of cells during gastrulation, in addition to dorsal mesoderm convergent extension, responsible for head-to-tail elongation. Finally, we demonstrate a functional interaction between Fry and NDR1 kinase, providing evidence of an evolutionarily conserved complex required for morphogenesis.

developmental biology↗

bioRxiv2019

Non-junctional Cadherin3 regulates cell migration and contact inhibition of locomotion via domain-dependent opposing regulations of Rac1.

Classical cadherins are well-known primary adhesion molecules responsible for physically connecting neighboring cells and signaling the cell-cell contact. Recent studies have suggested novel signaling roles for \"non-junctional\" cadherins (Niessen and Gottardi, 2008; Padmanabhan et al., 2017); however, the function of cadherin signaling independent of cell-cell contacts remains unknown. In this study, we used mesendoderm cells and tissues from gastrula stage Xenopus laevis embryos to demonstrate that extracellular and cytoplasmic cadherin domains regulate Rac1 in opposing directions in the absence of cell-cell contacts. Furthermore, we found that non-junctional cadherins regulate contact inhibition of locomotion (CIL) during gastrulation through alterations in the stability of the cytoskeleton. Live FRET imaging of Rac1 activity illustrated how non-junction cadherin3 (formerly C-cadherin) spatio-temporally regulates CIL. Our study provides novel insights into adhesion-independent signaling by cadherin3 and its role in regulating single and collective cell migration in vivo.

developmental biology↗

bioRxiv2019

Tissue mechanics drives epithelialization, goblet cell regeneration, and restoration of a mucociliated epidermis on the surface of embryonic aggregates.

Injury, surgery, and disease often disrupt tissues and it is the process of regeneration that aids the restoration of architecture and function. Regeneration can occur through multiple strategies including induction of stem cell expansion, transdifferentiation, or proliferation of differentiated cells. We have uncovered a case of regeneration that restores a mucociliated epithelium from mesenchymal cells. Following disruption of embryonic tissue architecture and assembly of a compact mesenchymal aggregate, regeneration first involves restoration of an epithelium, transitioning from mesenchymal cells at the surface of the aggregate. Cells establish apico-basal polarity within 5 hours and a mucociliated epithelium within 24. Regeneration coincides with nuclear translocation of the putative mechanotransducer YAP1 and a sharp increase in aggregate stiffness, and regeneration can be controlled by altering stiffness. We propose that regeneration of a mucociliated epithelium occurs in response to biophysical cues sensed by newly exposed cells on the surface of a disrupted mesenchymal tissue.

developmental biology↗