MacQuarrie, K. | Search bioRxiv

bioRxiv2026

Rab4 and Rab11 GTPases cooperate to reinforce adherens junctions at the leading edge to promote rapid embryonic wound healing

Collective cell movements drive the formation and repair of tissues and contribute to the spread of metastatic disease. Cells must remodel their cell-cell adhesions and actomyosin cytoskeleton to enable migration, but the mechanisms that drive these molecular rearrangements are unclear. We used wound healing in the Drosophila embryonic epidermis to investigate these mechanisms. Upon wounding, a supracellular cable composed of actin and myosin assembles around the wound. In parallel, adherens junction proteins, including E-cadherin, are depleted from the wound edge via endocytosis and accumulate at former tricellular junctions around the wound (wTCJs) through unknown mechanisms. We found that the small GTPases Rab4 and Rab11, implicated in endosomal trafficking, are necessary for rapid wound repair. Manipulations of Rab4 and Rab11 activity reduced wound closure rates but did not have effects on tissue mechanics or myosin polarization that could explain the defect. Instead, Rab4 and Rab11 redistributed E-cadherin to accumulate at wTCJs in a process necessary for collective cell movement. Together, our results show that adherens junction reinforcement via endosomal recycling is a key step of coordinated cell migration that controls the rate of wound healing independent of cytoskeletal remodeling. Summary StatementDuring embryonic wound repair, Rab4 and Rab11 GTPases transport E-cadherin to reinforce specialized cell adhesions at the wound edge, which are essential to drive rapid collective cell migration.

cell biology↗

bioRxiv2025

Geometrically encoded positioning of introns, intergenic segments, and exons in the human genome

Human tissues require a mechanism to generate durable, yet modifiable, transcriptional memories to sustain cell function across a lifetime. Previously, we demonstrated that nanoscale packing domains couple heterochromatin (cores) and euchromatin (outer zone) into unified reaction volumes that can generate transcriptional memory. In prior work, this framework demonstrated that RNA synthesis occurred within the ideal zone (intermediate density) portions of the domain. Naturally, this creates a question of where genes are positioned in relation to the packing domain architecture and which genetic material fills the domain core to sustain transcription. Here we propose that this could be solved by the encoded positioning of introns, intergenic segments, and exons as a projection of the functional packing layers of domains. This suggests that introns and intergenic segments are coupled to adjacent exons to generate coherent packing domain volumes. We illustrate how this organization would reconcile contradictions in epigenetic patterns, non-randomness in oncogenic mutations, and produce durable transcriptional memory. We conclude by showing that this genome geometry might have coincided with the rapid evolution of body-plan complexity, suggesting that chromatin geometry could be fundamental to metazoan evolution.

biophysics↗