title: Syntenin, a syndecan adaptor and an Arf6 phosphatidylinositol 4,5-bisphosphate effector, is essential for epiboly and gastrulation cell movements in zebrafish.
abstract: Epiboly, the spreading and the thinning of the blastoderm to cover the yolk cell and close the blastopore in fish embryos, is central to the process of gastrulation. Despite its fundamental importance, little is known about the molecular mechanisms that control this coordinated cell movement. By a combination of knockdown studies and rescue experiments in zebrafish (Danio rerio), we show that epiboly relies on the molecular networking of syntenin with syndecan heparan sulphate proteoglycans, which act as co-receptors for adhesion molecules and growth factors. Furthermore, we show that the interaction of syntenin with phosphatidylinositol 4,5-bisphosphate (PIP2) and with the small GTPase ADP-ribosylation factor 6 (Arf6), which regulate the endocytic recycling of syndecan, is necessary for epiboly progression. Analysis of the earliest cellular defects suggests a role for syntenin in the autonomous vegetal expansion of the yolk syncytial layer and the rearrangement of the actin cytoskeleton in extra-embryonic tissues, but not in embryonic cell fate determination. This study identifies the importance of the syntenin-syndecan-PIP2-Arf6 complex for the progression of fish epiboly and establishes its key role in directional cell movements during early development.
authors.affiliation: Laboratory for Signal Integration in Cell Fate Decision, Department of Human Genetics and VIB, K.U.Leuven, B-3000 Leuven,  Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Lambaerts
authors.forename: Stijn
authors.initials: S
authors.lastname: Van Dyck
authors.forename: Eva
authors.initials: E
authors.lastname: Mortier
authors.forename: Ylva
authors.initials: Y
authors.lastname: Ivarsson
authors.forename: Gisèle
authors.initials: G
authors.lastname: Degeest
authors.forename: Annouck
authors.initials: A
authors.lastname: Luyten
authors.forename: Elke
authors.initials: E
authors.lastname: Vermeiren
authors.forename: Bernard
authors.initials: B
authors.lastname: Peers
authors.forename: Guido
authors.initials: G
authors.lastname: David
authors.forename: Pascale
authors.initials: P
authors.lastname: Zimmermann
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D003599:Cytoskeleton / Q000235:genetics; D054262:Gastrulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D051379:Mice; D008969:Molecular Sequence Data; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D053667:Syndecans / Q000378:metabolism*; D053676:Syntenins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000089982:ADP-Ribosylation Factor 6; D019269:Phosphatidylinositol 4,5-Diphosphate; D053667:Syndecans; D053676:Syntenins; D029961:Zebrafish Proteins; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; C000715727:Arf6 protein, mouse