Phosphoinositide 3-kinase is required for process outgrowth and cell polarization of gastrulating mesendodermal cells.
BACKGROUND
During vertebrate gastrulation, cell polarization and migration are core components in the cellular rearrangements that lead to the formation of the three germ layers, ectoderm, mesoderm, and endoderm. Previous studies have implicated the Wnt/planar cell polarity (PCP) signaling pathway in controlling cell morphology and movement during gastrulation. However, cell polarization and directed cell migration are reduced but not completely abolished in the absence of Wnt/PCP signals; this observation indicates that other signaling pathways must be involved.


RESULTS
We show that Phosphoinositide 3-Kinases (PI3Ks) are required at the onset of zebrafish gastrulation in mesendodermal cells for process formation and cell polarization. Platelet Derived Growth Factor (PDGF) functions upstream of PI3K, while Protein Kinase B (PKB), a downstream effector of PI3K activity, localizes to the leading edge of migrating mesendodermal cells. In the absence of PI3K activity, PKB localization and cell polarization are strongly reduced in mesendodermal cells and are followed by slower but still highly coordinated and directed movements of these cells.


CONCLUSIONS
We have identified a novel role of a signaling pathway comprised of PDGF, PI3K, and PKB in the control of morphogenetic cell movements during gastrulation. Furthermore, our findings provide insight into the relationship between cell polarization and directed cell migration at the onset of zebrafish gastrulation.
Montero
Juan-Antonio
JA
Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307, Dresden, Germany.
Kilian
Beate
B
Chan
Joanne
J
Bayliss
Peter E
PE
Heisenberg
Carl-Philipp
CP
D000818:Animals; D001483:Base Sequence; D016764:Cell Polarity / Q000502:physiology*; D004707:Endoderm / Q000502:physiology*; D005775:Gastrula / Q000166:cytology / Q000502:physiology*; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D008845:Microinjections; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism* / Q000502:physiology; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology*
D019869:Phosphatidylinositol 3-Kinases