title: Ptenb mediates gastrulation cell movements via Cdc42/AKT1 in zebrafish.
abstract: Phosphatidylinositol 3-kinase (PI3 kinase) mediates gastrulation cell migration in zebrafish via its regulation of PIP(2)/PIP(3) balance. Although PI3 kinase counter enzyme PTEN has also been reported to be essential for gastrulation, its role in zebrafish gastrulation has been controversial due to the lack of gastrulation defects in pten-null mutants. To clarify this issue, we knocked down a pten isoform, ptenb by using anti-sense morpholino oligos (MOs) in zebrafish embryos and found that ptenb MOs inhibit convergent extension by affecting cell motility and protrusion during gastrulation. The ptenb MO-induced convergence defect could be rescued by a PI3-kinase inhibitor, LY294002 and by overexpressing dominant negative Cdc42. Overexpression of human constitutively active akt1 showed similar convergent extension defects in zebrafish embryos. We also observed a clear enhancement of actin polymerization in ptenb morphants under cofocal microscopy and in actin polymerization assay. These results suggest that Ptenb by antagonizing PI3 kinase and its downstream Akt1 and Cdc42 to regulate actin polymerization that is critical for proper cell motility and migration control during gastrulation in zebrafish.
authors.affiliation: Institute of Zoology, National Taiwan University, Taipei, Taiwan, Republic of China.
authors.forename: Chen-Min
authors.initials: CM
authors.lastname: Yeh
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Liu
authors.forename: Ching-Jen
authors.initials: CJ
authors.lastname: Chang
authors.forename: Shih-Lei
authors.initials: SL
authors.lastname: Lai
authors.forename: Chung-Der
authors.initials: CD
authors.lastname: Hsiao
authors.forename: Shyh-Jye
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D047108:Embryonic Development / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D054262:Gastrulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000378:metabolism*; D058105:Polymerization / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000172:deficiency / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D016376:Oligonucleotides, Antisense; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010749:Phosphoprotein Phosphatases; D051057:Proto-Oncogene Proteins c-akt; D029961:Zebrafish Proteins; D020764:cdc42 GTP-Binding Protein; C511365:Ptenb protein, zebrafish