Filopodia-based contact stimulation of cell migration drives tissue morphogenesis

Abstract

Cells migrate collectively to form tissues and organs during morphogenesis. Contact inhibition of locomotion (CIL) drives collective migration by inhibiting lamellipodial protrusions at cell–cell contacts and promoting polarization at the leading edge. Here, we report a CIL-related collective cell behavior of myotubes that lack lamellipodial protrusions, but instead use filopodia to move as a cohesive cluster in a formin-dependent manner. We perform genetic, pharmacological and mechanical perturbation analyses to reveal the essential roles of Rac2, Cdc42 and Rho1 in myotube migration. These factors differentially control protrusion dynamics and cell–matrix adhesion formation. We also show that active Rho1 GTPase localizes at retracting free edge filopodia and that Rok-dependent actomyosin contractility does not mediate a contraction of protrusions at cell–cell contacts, but likely plays an important role in the constriction of supracellular actin cables. Based on these findings, we propose that contact-dependent asymmetry of cell–matrix adhesion drives directional movement, whereas contractile actin cables contribute to the integrity of the migrating cell cluster.

Poria cocos Regulates Cell Migration and Actin Filament Aggregation in B35 and C6 Cells by Modulating the RhoA, CDC42, and Rho Signaling Pathways

“…The phosphorylation of MLC2 will then induce myosin activation and stress fiber contraction in cells [ 36 , 37 ]. In addition, the RhoA protein can regulate the expression of ARP2/3 to control cell filopodia and migration [ 38 , 39 ]. CDC42-induced PAK1/N-WASP activation can also regulate ARP2/3-mediated cytoskeletal remodeling [ 40 ].…”

From the Matrix to the Nucleus and Back: Mechanobiology in the Light of Health, Pathologies, and Regeneration of Oral Periodontal Tissues

“…The actin cytoskeleton as the central hub of AJs, FAs, and NMT signaling is another interesting target to be addressed by intervention strategies for periodontal tissue regeneration [350,351]. The difference in addressing AJs or FAs on the cellular surface is that RhoA, Rac1, Cdc42 or ROCK cannot be modulated via direct interaction with a biomaterial.…”

Collective cell migration driven by filopodia—New insights from the social behavior of myotubes

“…Recently, the testis myotube migration system was introduced. [ 4 ] To put it into context, some well‐established models will be summarized in this section followed by a description of the myotube system highlighting new concepts of self‐regulation in collective cell migration.…”

“…Detailed observation employing live‐cell 4D imaging of cultured pupal Drosophila testis revealed that myotubes seem likewise mesenchymal and homogeneous. [ 4 ] Before migration starts, until 28–30 h after pupae formation (APF), the anlagen of the testis and the rest of the genital tract lie separately inside the body cavity. The so‐called genital imaginal disc contains myoblasts that later build the musculature of the entire system.…”

“…However, close examination of the migrating myotubes employing the newly established 4D imaging methods revealed that all myotubes resembled each other in terms of cell protrusion. [ 4 ] Unlike border cell migration, no subset of cells seemed to exclusively react to an outside gradient. Instead, myotubes likely self‐regulate their behavior.…”