RPTPα and PTPε signaling via Fyn/Yes and RhoA is essential for zebrafish convergence and extension cell movements during gastrulation

Eekelen, Mark van; Runtuwene, Vincent; Overvoorde, John; Hertog, Jeroen den

doi:10.1016/j.ydbio.2010.02.026

Cited by 19 publications

(26 citation statements)

References 57 publications

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“…4C). These defects point to impaired convergent extension (CE) movements during gastrulation and have indeed been observed in embryos of well-established CE regulators such as Wnt/PCP signaling (Topczewski et al, 2001; van Eekelen et al, 2010). To rule out that these CE defects arose due to non-specific effects of co-injection of ctnna1 morpholino with the mRNAs, we injected either α-catenin-GFP or α-catenin-ΔVBS-GFP mRNA in embryos from a heterozygous ctnna1 mutant incross.…”

Section: Resultsmentioning

confidence: 98%

αE-catenin-dependent mechanotransduction is essential for proper convergent extension in zebrafish

et al. 2016

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Cadherin complexes mediate cell-cell adhesion and are crucial for embryonic development. Besides their structural function, cadherin complexes also transduce tension across the junction-actomyosin axis into proportional biochemical responses. Central to this mechanotransduction is the stretching of the cadherin-F-actin-linker α-catenin, which opens its central domain for binding to effectors such as vinculin. Mechanical unfolding of α-catenin leads to force-dependent reinforcement of cadherin-based junctions as studied in cell culture. The importance of cadherin mechanotransduction for embryonic development has not been studied yet. Here we used TALEN-mediated gene disruption to perturb endogenous αE-catenin in zebrafish development. Zygotic α-catenin mutants fail to maintain their epithelial barrier, resulting in tissue rupturing. We then specifically disrupted mechanotransduction, while maintaining cadherin adhesion, by expressing an αE-catenin construct in which the mechanosensitive domain was perturbed. Expression of either wild-type or mechano-defective α-catenin fully rescues barrier function in α-catenin mutants; however, expression of mechano-defective α-catenin also induces convergence and extension defects. Specifically, the polarization of cadherin-dependent, lamellipodia-driven cell migration of the lateral mesoderm was lost. These results indicate that cadherin mechanotransduction is crucial for proper zebrafish morphogenesis, and uncover one of the essential processes affected by its perturbation.

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Section: Resultsmentioning

confidence: 98%

αE-catenin-dependent mechanotransduction is essential for proper convergent extension in zebrafish

et al. 2016

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“…In situ hybridizations were performed as described by Thisse et al (32). The bmp2b, chd, gsc, ntla, dlx3, hgg, krox20, and myod probes were described previously (11,33). Antisense and sense Mpzl1 probes, respectively, were synthesized by T7 and SP6 mRNA polymerase (Promega) from pCS2ϩPZR.…”

Section: Methodsmentioning

confidence: 99%

PZR Coordinates Shp2 Noonan and LEOPARD Syndrome Signaling in Zebrafish and Mice

Overman

Bonetti

et al. 2014

Molecular and Cellular Biology

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g Noonan syndrome (NS) is an autosomal dominant disorder caused by activating mutations in the PTPN11 gene encoding Shp2, which manifests in congenital heart disease, short stature, and facial dysmorphia. The complexity of Shp2 signaling is exemplified by the observation that LEOPARD syndrome (LS) patients possess inactivating PTPN11 mutations yet exhibit similar symptoms to NS. Here, we identify "protein zero-related" (PZR), a transmembrane glycoprotein that interfaces with the extracellular matrix to promote cell migration, as a major hyper-tyrosyl-phosphorylated protein in mouse and zebrafish models of NS and LS. PZR hyper-tyrosyl phosphorylation is facilitated in a phosphatase-independent manner by enhanced Src recruitment to NS and LS Shp2. In zebrafish, PZR overexpression recapitulated NS and LS phenotypes. PZR was required for zebrafish gastrulation in a manner dependent upon PZR tyrosyl phosphorylation. Hence, we identify PZR as an NS and LS target. Enhanced PZR-mediated membrane recruitment of Shp2 serves as a common mechanism to direct overlapping pathophysiological characteristics of these PTPN11 mutations.

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“…We previously showed that RPTPα and PTPε function in C/E cell movements by activation of the SFKs, Fyn and Yes [45], [46]. We assessed the effects of expression of constitutively active mutants of Fyn and Yes that harbor point mutations (Tyr to Phe) in their inhibitory C-terminal phosphorylation sites on C/E cell movements.…”

Section: Resultsmentioning

confidence: 99%

“…In order to investigate if cell polarization is causing the observed phenotypes, we determined the shapes of dorsally migrating presomitic cells as described before [45]. Wildtype or knockdown embryos were (co-)injected with YFP-caax mRNA and mCherry-H2B to label the cell membrane and nuclei, respectively.…”

Section: Resultsmentioning

confidence: 99%

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Pair-Wise Regulation of Convergence and Extension Cell Movements by Four Phosphatases via RhoA

et al. 2012

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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.

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RPTPα and PTPε signaling via Fyn/Yes and RhoA is essential for zebrafish convergence and extension cell movements during gastrulation

Cited by 19 publications

References 57 publications

αE-catenin-dependent mechanotransduction is essential for proper convergent extension in zebrafish

αE-catenin-dependent mechanotransduction is essential for proper convergent extension in zebrafish

PZR Coordinates Shp2 Noonan and LEOPARD Syndrome Signaling in Zebrafish and Mice

Pair-Wise Regulation of Convergence and Extension Cell Movements by Four Phosphatases via RhoA

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