title: Pair-wise regulation of convergence and extension cell movements by four phosphatases via RhoA.
abstract: Various signaling pathways regulate shaping of the main body axis during early vertebrate development. Here, we focused on the role of protein-tyrosine phosphatase signaling in convergence and extension cell movements. We identified Ptpn20 as a structural paralogue of PTP-BL and both phosphatases were required for normal gastrulation cell movements. Interestingly, knockdowns of PTP-BL and Ptpn20 evoked similar developmental defects as knockdown of RPTPα and PTPε. Co-knockdown of RPTPα and PTP-BL, but not Ptpn20, had synergistic effects and conversely, PTPε and Ptpn20, but not PTP-BL, cooperated, demonstrating the specificity of our approach. RPTPα and PTPε knockdowns were rescued by constitutively active RhoA, whereas PTP-BL and Ptpn20 knockdowns were rescued by dominant negative RhoA. Consistently, RPTPα and PTP-BL had opposite effects on RhoA activation, both in a PTP-dependent manner. Downstream of the PTPs, we identified NGEF and Arhgap29, regulating RhoA activation and inactivation, respectively, in convergence and extension cell movements. We propose a model in which two phosphatases activate RhoA and two phosphatases inhibit RhoA, resulting in proper cell polarization and normal convergence and extension cell movements.
authors.affiliation: Hubrecht Institute and University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: van Eekelen
authors.forename: Vincent
authors.initials: V
authors.lastname: Runtuwene
authors.forename: Wouter
authors.initials: W
authors.lastname: Masselink
authors.forename: Jeroen
authors.initials: J
authors.lastname: den Hertog
mesh_terms: D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D054262:Gastrulation; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029961:Zebrafish Proteins; D017027:Protein Tyrosine Phosphatases; D020559:Monomeric GTP-Binding Proteins; C549425:rhoab protein, zebrafish