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Abstract How a developing organ robustly coordinates the cellular mechanics and growth to reach a final size and shape remains poorly understood. Through iterations between experiments and model simulations that include a mechanistic description of interkinetic nuclear migration, we show that the local curvature, height, and nuclear positioning of cells in theDrosophilawing imaginal disc are defined by the concurrent patterning of actomyosin contractility, cell-ECM adhesion, ECM stiffness, and interfacial membrane tension. We show that increasing cell proliferation via different growth-promoting pathways results in two distinct phenotypes. Triggering proliferation through insulin signaling increases basal curvature, but an increase in growth through Dpp signaling and Myc causes tissue flattening. These distinct phenotypic outcomes arise from differences in how each growth pathway regulates the cellular cytoskeleton, including contractility and cell-ECM adhesion. The coupled regulation of proliferation and cytoskeletal regulators is a general strategy to meet the multiple context-dependent criteria defining tissue morphogenesis.
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This content will become publicly available on September 5, 2026
An ancient and essential miRNA family controls cellular interaction pathways in C. elegans
The transition from unicellular to multicellular life required the acquisition of coordinated and regulated cellular behaviors, including adhesion and migration. In metazoans, this involves adhesion proteins, signaling systems, and an elaborate extracellular matrix (ECM) that contributes to adhesion and signaling interactions. Innovations that enabled complex multicellularity occurred through new genes in these pathways, novel functions for existing genes, and regulatory changes. Gene regulation by microRNAs (miRNAs) expanded with multicellularity. A single miRNA, miR-100, arose in the last common eumetazoan ancestor and is widely conserved across animals. We reveal the molecular function of itsC. eleganshomolog, the miR-51 family. This family acts in a dose-dependent manner to control morphogenesis by regulating several genes involved in cell signaling, adhesion, and migration, including ECM modifiers—specifically heparan sulfate sulfotransferases (HSTs). Some of these targets are also predicted to be conserved targets across vertebrates. Our work suggests that this miRNA provided an innovation in the regulation of cellular interactions early in metazoan evolution.
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- Award ID(s):
- 2238425
- PAR ID:
- 10660277
- Publisher / Repository:
- AAAS
- Date Published:
- Journal Name:
- Science Advances
- Volume:
- 11
- Issue:
- 36
- ISSN:
- 2375-2548
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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