Molecular basis of cell migration in the fish lateral line: Role of the chemokine receptor CXCR4 and of its ligand, SDF1

Abstract

Cell migration plays an essential role in many morphogenetic processes, and its deregulation has many dramatic consequences. Yet how migration is controlled during normal development is still a largely unresolved question. We examined this process in the case of the posterior lateral line (PLL), a mechanosensory system present in fish and amphibians. In zebrafish, the embryonic PLL comprises seven to eight sense organs (neuromasts) aligned from head to tail along the flank of the animal and is formed by a primordium that originates from a cephalic placode. This primordium migrates along a stereotyped pathway toward the tip of the tail and deposits in its wake discrete groups of cells, each of which will become a neuromast. We show that a trail of SDF1-like chemokine is present along the pathway of the primordium and that a CXCR4-like chemokine receptor is expressed by the migrating cells. The inactivation of either the ligand or its receptor blocks migration, whereas in mutants in which the normal SDF1 trail is absent, the primordium path is redirected to the next, more ventral sdf1 expression domain. In all cases, the sensory axons remain associated to the primordium, indicating that the extension of the neurites to form the PLL nerve depends on the movement of the primordium. We conclude that both the formation and the innervation of this system depend on the SDF1-CXCR4 system, which has also been implicated in several migration events in humans, including metastasis formation and lymphocyte homing.

Initial specification of the epibranchial placode in zebrafish embryos depends on the fibroblast growth factor signal

“…Finally, we observed that the sox3-expressing p4 subdomain migrates posteriorly from its original domain along the body axis after the 20-somite stage (data not shown). Given that this migration trend of the p4 subdomain is similar to that of the posterior lateral line primordium, as revealed by morphological observation (Laguerre et al, 2005) and expression of the chemokine receptor cxcr4 (Chong et al, 2001;David et al, 2002), we suggest that the p4 subdomain represents the anlage of the posterior lateral line system.…”

Molecular cloning and embryonic expression of zebrafish PCSK5 co‐orthologues: Functional assessment during lateral line development

“…It has been shown that migration of the posterior lateral line primordium depends on the interaction between CXCR4 (chemokine receptor) and its ligand SDF1 (stromal-derived factor). While the migrating cells express CXCR4, its ligand SDF1 is found in the horizontal myoseptum (David et al, 2002). The same mechanism is reported in mouse germ cell migration and survival (Molyneaux et al, 2003).…”

lef1 controls patterning and proliferation in the posterior lateral line system of zebrafish

“…The embryonic PLL is generated by a sensory primordium, which migrates along a defined pathway, from the head to the tip of the tail (Harrison, 1904;Stone, 1937;Metcalfe, 1985). In zebrafish, primordium migration depends on SDF1 signaling by cells along the path of migration (David et al, 2002;Li et al, 2004;Haas and Gilmour, 2006; reviewed in Ghysen and Dambly-Chaudière, 2007). The direction of migration depends on the anisotropic distribution of two SDF1 receptors, CXCR4 which is present in the leading two-thirds of the primordium, and CXCR7 which is present in the trailing third Valentin et al, 2007).…”

“…Whereas the binding of SDF1 to CXCR4 drives the migration (David et al, 2002), CXCR7 acts as an atypical receptor (Comerford et al, 2007) that may sequester SDF1 (Balabanian et al, 2005) in the trailing region of the primordium and thereby provide directionality to the migration . Alternatively or additionally, CXCR7 may contribute to migration independently of CXCR4 (Valentin et al, 2007).…”