title: Generation and dynamics of an endogenous, self-generated signaling gradient across a migrating tissue.
abstract: In animals, many cells reach their destinations by migrating toward higher concentrations of an attractant. However, the nature, generation, and interpretation of attractant gradients are poorly understood. Using a GFP fusion and a signaling sensor, we analyzed the distribution of the attractant chemokine Sdf1 during migration of the zebrafish posterior lateral line primordium, a cohort of about 200 cells that migrates over a stripe of cells uniformly expressing sdf1. We find that a small fraction of the total Sdf1 pool is available to signal and induces a linear Sdf1-signaling gradient across the primordium. This signaling gradient is initiated at the rear of the primordium, equilibrates across the primordium within 200 min, and operates near steady state. The rear of the primordium generates this gradient through continuous sequestration of Sdf1 protein by the alternate Sdf1-receptor Cxcr7. Modeling shows that this is a physically plausible scenario.
authors.affiliation: Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Gayatri
authors.initials: G
authors.lastname: Venkiteswaran
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Lewellis
authors.forename: John
authors.initials: J
authors.lastname: Wang
authors.forename: Eric
authors.initials: E
authors.lastname: Reynolds
authors.forename: Charles
authors.initials: C
authors.lastname: Nicholson
authors.forename: Holger
authors.initials: H
authors.lastname: Knaut
mesh_terms: D000818:Animals; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000032:analysis; D006801:Humans; D053403:Lateral Line System / Q000196:embryology*; D008954:Models, Biological; D009024:Morphogenesis; D054387:Receptors, CXCR / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: C519524:CXCR7 protein, zebrafish; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D029961:Zebrafish Proteins; C579453:cxcl12a protein, zebrafish; D049452:Green Fluorescent Proteins