3 research outputs found
Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma
The mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies and mesothelioma tumors. Nonetheless, the embryonic emergence of mesothelia remains incompletely understood. Here, we track mesothelial origins in the lateral plate mesoderm (LPM) using zebrafish. Single-cell transcriptomics uncovers a post-gastrulation gene expression signature centered on hand2 in distinct LPM progenitor cells. We map mesothelial progenitors to lateral-most, hand2-expressing LPM and confirm conservation in mouse. Time-lapse imaging of zebrafish hand2 reporter embryos captures mesothelium formation including pericardium, visceral, and parietal peritoneum. We find primordial germ cells migrate with the forming mesothelium as ventral migration boundary. Functionally, hand2 loss disrupts mesothelium formation with reduced progenitor cells and perturbed migration. In mouse and human mesothelioma, we document expression of LPM-associated transcription factors including Hand2, suggesting re-initiation of a developmental program. Our data connects mesothelium development to Hand2, expanding our understanding of mesothelial pathologies
Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma.
The mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies and mesothelioma tumors. Nonetheless, the embryonic emergence of mesothelia remains incompletely understood. Here, we track mesothelial origins in the lateral plate mesoderm (LPM) using zebrafish. Single-cell transcriptomics uncovers a post-gastrulation gene expression signature centered on hand2 in distinct LPM progenitor cells. We map mesothelial progenitors to lateral-most, hand2-expressing LPM and confirm conservation in mouse. Time-lapse imaging of zebrafish hand2 reporter embryos captures mesothelium formation including pericardium, visceral, and parietal peritoneum. We find primordial germ cells migrate with the forming mesothelium as ventral migration boundary. Functionally, hand2 loss disrupts mesothelium formation with reduced progenitor cells and perturbed migration. In mouse and human mesothelioma, we document expression of LPM-associated transcription factors including Hand2, suggesting re-initiation of a developmental program. Our data connects mesothelium development to Hand2, expanding our understanding of mesothelial pathologies
Highly-Efficient Guiding of Motile Microtubules on Non-Topographical Motor Patterns
Molecular motors,
highly efficient biological nanomachines, hold
the potential to be employed for a wide range of nanotechnological
applications. Toward this end, kinesin, dynein, or myosin motor proteins
are commonly surface-immobilized within engineered environments in
order to transport cargo attached to cytoskeletal filaments. Being
able to flexibly control the direction of filament motion, and in
particular on planar, non-topographical surfaces, has, however, remained
challenging. Here, we demonstrate the applicability of a UV-laser-based
ablation technique to programmably generate highly localized patterns
of functional kinesin-1 motors with different shapes and sizes on
PLL-<i>g</i>-PEG-coated polystyrene surfaces. Straight and
curved motor tracks with widths of less than 500 nm could be generated
in a highly reproducible manner and proved to reliably guide gliding
microtubules. Though dependent on track curvature, the characteristic
travel lengths of the microtubules on the tracks significantly exceeded
earlier predictions. Moreover, we experimentally verified the performance
of complex kinesin-1 patterns, recently designed by evolutionary algorithms
for controlling the global directionality of microtubule motion on
large-area substrates