Zebrafish Posterior Lateral Line primordium migration requires interactions between a superficial sheath of motile cells and the skin

Abstract

The Zebrafish Posterior Lateral Line primordium migrates in a channel between the skin and somites. Its migration depends on the coordinated movement of its mesenchymal-like leading cells and trailing cells, which form epithelial rosettes, or protoneuromasts. We describe a superficial population of flat primordium cells that wrap around deeper epithelialized cells and extend polarized lamellipodia to migrate apposed to the overlying skin. Polarization of lamellipodia extended by both superficial and deeper protoneuromast-forming cells depends on Fgf signaling. Removal of the overlying skin has similar effects on superficial and deep cells: lamellipodia are lost, blebs appear instead, and collective migration fails. When skinned embryos are embedded in Matrigel, basal and superficial lamellipodia are recovered; however, only the directionality of basal protrusions is recovered, and migration is not rescued. These observations support a key role played by superficial primordium cells and the skin in directed migration of the Posterior Lateral Line primordium.

Rear traction forces drive adherent tissue migration in vivo

“…We also detected short-lived Itgb1b-sfGFP clusters on the apical side of the superficial cells ( Extended Data Fig. 4a )—a layer of thin primordium cells that face the skin 8 , 13 . These clusters are probably induced by Fibronectin or proteoglycans—labeled by chondroitin sulfate—that are expressed around the primordium ( Extended Data Figure 1k , l ).…”

“…If the skin and the BM serve as substrates for the primordium, they should also be required for the migration of the primordium. Indeed, surgical removal of the skin blocks primordium migration 8 . To assess the role of the skin in primordium migration in a less invasive manner, we depleted α-catenin tagged with Citrine (Ctnna1-Citrine) in the primordium using the degron system zGrad 9 expressed from the cxcr4b promoter in the migrating primordium ( Extended Data Fig.…”

Dnmt1 is required for the development of auditory organs via cell cycle arrest and Fgf signalling

“…In recent years, several mechanisms have been revealed to be corelated with the oriented migration of primordium 28,30 . As previously reported, blocking Fgf signalling by constructing fgf3 ; fgf10 double morphants, Fgf special inhibitor SU5402 or heat‐shock inducible Fgfr1 depletion can severely reduce the migrating speed of primordium 30 and change the directionality of migrating cells 40 . Wnt/β‐catenin and Fgf signalling are also involved in primordium migration of zebrafish through regulating the chemokine signalling pathway components cxcr4b and cxcr7b 28 .…”

“…28,30 As previously reported, blocking Fgf signalling by constructing fgf3; fgf10 double morphants, Fgf special inhibitor SU5402 or heat-shock inducible Fgfr1 depletion can severely reduce the migrating speed of primordium 30 and change the directionality of migrating cells. 40 Wnt/β-catenin and Fgf signalling are also involved in primordium migration of zebrafish through regulating the chemokine signalling pathway components cxcr4b and cxcr7b. 28 Consistent with the literature, this study revealed that knockdown of Dnmt1 inhibited the primordium migration and neuromast maturation through differently regulating the Fgf, Wnt and chemokine signalling pathways that the transcript levels of fgf3, fgf10, pea3, cxcr4b and cxcl12 were significantly decreased, while the expression levels of lef1 and cxcr7b were significantly increased in Dnmt1-MO morphants compared to the controls.…”

Matrix topology guides collective cell migration in vivo

“…This active rim migration is driven by cryptopodia, which are defined as basal protrusions that extend beneath the next cell along the direction of migration ( 22 ). These have so far mainly been reported in vitro ( 22, 23 ) but recently they have also been suspected to be involved in some types of collective cell migration in vivo ( 33, 34 ). In ‘closed’ epithelial structures in vitro that lack a free edge or clearly defined leader and follower cells, the direction and angle of contact of cryptopodia with the underlying substrate predetermines the overall direction of migration ( 23 ).…”