title: Leading and trailing cells cooperate in collective migration of the zebrafish posterior lateral line primordium.
abstract: Collective migration of cells in the zebrafish posterior lateral line primordium (PLLp) along a path defined by Cxcl12a expression depends on Cxcr4b receptors in leading cells and on Cxcr7b in trailing cells. Cxcr7b-mediated degradation of Cxcl12a by trailing cells generates a local gradient of Cxcl12a that guides PLLp migration. Agent-based computer models were built to explore how a polarized response to Cxcl12a, mediated by Cxcr4b in leading cells and prevented by Cxcr7b in trailing cells, determines unidirectional migration of the PLLp. These chemokine signaling-based models effectively recapitulate many behaviors of the PLLp and provide potential explanations for the characteristic behaviors that emerge when the PLLp is severed by laser to generate leading and trailing fragments. As predicted by our models, the bilateral stretching of the leading fragment is lost when chemokine signaling is blocked in the PLLp. However, movement of the trailing fragment toward the leading cells, which was also thought to be chemokine dependent, persists. This suggested that a chemokine-independent mechanism, not accounted for in our models, is responsible for this behavior. Further investigation of trailing cell behavior shows that their movement toward leading cells depends on FGF signaling and it can be re-oriented by exogenous FGF sources. Together, our observations reveal the simple yet elegant manner in which leading and trailing cells coordinate migration; while leading cells steer PLLp migration by following chemokine cues, cells further back play follow-the-leader as they migrate toward FGFs produced by leading cells.
authors: Section on Neural Developmental Dynamics, Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2790, USA.
authors: Damian
authors: D
authors: Dalle Nogare
authors: Section on Neural Developmental Dynamics, Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2790, USA.
authors: Katherine
authors: K
authors: Somers
authors: Section on Neural Developmental Dynamics, Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2790, USA.
authors: Swetha
authors: S
authors: Rao
authors: Section on Neural Developmental Dynamics, Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2790, USA Department of Cell Biology and Molecular Medicine, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ 17101-1709, USA.
authors: Miho
authors: M
authors: Matsuda
authors: Institute of Cell Biology, Center for Molecular Biology of Inflammation, 48149 Münster, Germany.
authors: Michal
authors: M
authors: Reichman-Fried
authors: Institute of Cell Biology, Center for Molecular Biology of Inflammation, 48149 Münster, Germany.
authors: Erez
authors: E
authors: Raz
authors: Section on Neural Developmental Dynamics, Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2790, USA chitnisa@mail.nih.gov.
authors: Ajay B
authors: AB
authors: Chitnis
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002450:Cell Communication; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000502:physiology; D018925:Chemokines / Q000378:metabolism; D003198:Computer Simulation; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053403:Lateral Line System / Q000196:embryology*; D054387:Receptors, CXCR / Q000502:physiology; D019718:Receptors, CXCR4 / Q000502:physiology; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000502:physiology
chemical_list: C471276:CXCR4b protein, zebrafish; C519524:CXCR7 protein, zebrafish; D054377:Chemokine CXCL12; D018925:Chemokines; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D029961:Zebrafish Proteins; C579453:cxcl12a protein, zebrafish; D005346:Fibroblast Growth Factors
keywords: Agent-based modeling; Chemokines; Collective migration; FGF; Lateral line; Zebrafish