[PDF][PDF] The chemokine SDF1a coordinates tissue migration through the spatially restricted activation of Cxcr7 and Cxcr4b

G Valentin, P Haas, D Gilmour - Current Biology, 2007 - cell.com
G Valentin, P Haas, D Gilmour
Current Biology, 2007cell.com
Tissue migration is a collective behavior that plays a key role in the formation of many organ
systems [1–3]. Although tissue movements are guided by extrinsic cues, in many contexts,
their receptors need to be active only at the leading edge to ensure morphogenesis [4–8].
This has led to the prevalent view that extrinsic signals exert their influence by controlling a
small number of leader cells. The zebrafish lateral-line primordium is a cohesive cohort of
over 100 cells that is guided through CXCR4-SDF1 signaling [9–11]. Recent work has …
Summary
Tissue migration is a collective behavior that plays a key role in the formation of many organ systems [1–3]. Although tissue movements are guided by extrinsic cues, in many contexts, their receptors need to be active only at the leading edge to ensure morphogenesis [4–8]. This has led to the prevalent view that extrinsic signals exert their influence by controlling a small number of leader cells. The zebrafish lateral-line primordium is a cohesive cohort of over 100 cells that is guided through CXCR4-SDF1 signaling [9–11]. Recent work has shown that Cxcr4b activity is only required in cells at the very tip, raising the question of what controls cell behavior within trailing regions [6]. Here, we present the first mutant in zebrafish SDF1a/CXCL12a and show, surprisingly, that the resultant phenotype is stronger than a null mutation in its cognate receptor, Cxcr4b, indicating the involvement of other SDF1a receptors. A candidate approach identified Cxcr7/RDC1, whose expression is restricted to cells behind the leading edge. Morpholino knockdown of Cxcr7 leads to a novel phenotype in which the migration of trailing cells is specifically affected, causing tissue stretching, a defect rescued by the reintroduction of wild-type cells specifically at the back of the primordium. Finally, we present evidence that Cxcr4b and Cxcr7 act independently to regulate group migration. We provide the first example where a single extrinsic guidance cue, SDF1a, directly controls the migration of both leading and trailing edges of a tissue through the activation of two independent receptors, CXCR4b and CXCR7.
cell.com