Pair-wise regulation of convergence and extension cell movements by four phosphatases via RhoA

TY - JOUR

T1 - Pair-wise regulation of convergence and extension cell movements by four phosphatases via RhoA

AU - van Eekelen, M.

AU - Runtuwene, V.

AU - Masselink, W.

AU - den Hertog, J.

N1 - Reporting year: 2012

PY - 2012

Y1 - 2012

N2 - 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 RPTPalpha and PTPepsilon. Co-knockdown of RPTPalpha and PTP-BL, but not Ptpn20, had synergistic effects and conversely, PTPepsilon and Ptpn20, but not PTP-BL, cooperated, demonstrating the specificity of our approach. RPTPalpha and PTPepsilon knockdowns were rescued by constitutively active RhoA, whereas PTP-BL and Ptpn20 knockdowns were rescued by dominant negative RhoA. Consistently, RPTPalpha 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.

AB - 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 RPTPalpha and PTPepsilon. Co-knockdown of RPTPalpha and PTP-BL, but not Ptpn20, had synergistic effects and conversely, PTPepsilon and Ptpn20, but not PTP-BL, cooperated, demonstrating the specificity of our approach. RPTPalpha and PTPepsilon knockdowns were rescued by constitutively active RhoA, whereas PTP-BL and Ptpn20 knockdowns were rescued by dominant negative RhoA. Consistently, RPTPalpha 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.

U2 - 10.1371/journal.pone.0035913

DO - 10.1371/journal.pone.0035913

M3 - Article

SN - 1932-6203

VL - 7

SP - 35913

JO - PLoS One

JF - PLoS One

IS - 4

ER -