Abstract
BackgroundThe formation of the posterior lateral line of teleosts depends on the migration of a primordium that originates near the otic vesicle and moves to the tip of the tail. Groups of cells at the trailing edge of the primordium slow down at regular intervals and eventually settle to differentiate as sense organs. The migration of the primordium is driven by the chemokine SDF1 and by its receptor CXCR4, encoded respectively by the genes sdf1a and cxcr4b. cxcr4b is expressed in the migrating cells and is down-regulated in the trailing cells of the primordium. sdf1a is expressed along the path of migration. There is no evidence for a gradient of sdf1a expression, however, and the origin of the directionality of migration is not known.ResultsHere we document the expression of a second chemokine receptor gene, cxcr7, in the migrating primordium. We show that cxcr7 is highly expressed in the trailing cells of the primordium but not at all in the leading cells, a pattern that is complementary to that of cxcr4b. Even though cxcr7 is not expressed in the cells that lead primordium migration, its inactivation results in impaired migration. The phenotypes of cxcr4b, cxcr7 double morphant embryos suggest, however, that CXCR7 does not contribute to the migratory capabilities of primordium cells. We also show that, in the absence of cxcr4b, expression of cxcr7 becomes ubiquitous in the stalled primordium.ConclusionOur observations suggest that CXCR7 is required to provide directionality to the migration. We propose that directionality is imposed on the primordium as soon as it comes in contact with the stripe of SDF1, and is maintained throughout migration by a negative interaction between the two receptors.
Highlights
The formation of the posterior lateral line of teleosts depends on the migration of a primordium that originates near the otic vesicle and moves to the tip of the tail
Identification of cxcr7, a gene potentially involved in the control of posterior lateral line (PLL) primordium migration We recognized cxcr7 as an EST potentially involved in the control of PLL primordium migration based on its pattern of expression ([16] and see Material and Methods)
Sequence comparisons revealed that this EST corresponds to a gene that encodes the homolog of the mammalian chemokine receptor, CXCR7
Summary
The formation of the posterior lateral line of teleosts depends on the migration of a primordium that originates near the otic vesicle and moves to the tip of the tail. Cxcr4b is expressed in the migrating cells and is down-regulated in the trailing cells of the primordium. Directed cell migration is involved in many aspects of development including the establishment of the embryonic body plan, organogenesis and organ function. It plays a role in several pathological processes, notably the spread of tumour cells and formation of metastases. Most work on cell migration relies on in vitro systems where migration is relatively easy to monitor and quantify. This has led to substantial (page number not for citation purposes). Migration is crucially dependent on the cell environment, and ideally one would like to study its control in a system where migration can be visualized in vivo and in real time
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