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.
Highlights
Vertebrate embryonic development is characterized by three processes, cell proliferation, differentiation and migration
Upon further investigation we found a gene named frmpd2 or a gene with similar structure to the 59 side of ptpn20 in all species, including the human genome which according to the Ensembl database contains 3 copies of ptpn20; ptpn20a, ptpn20b and ptpn20c, all accompanied with their own frmpd2-(like) gene
Here, we describe four protein tyrosine phosphatase (PTP) involved in regulating cell polarity in zebrafish convergence and extension (C/E) cell movements, RPTPa, PTPe, PTP-BL and Ptpn20 (Fig. 2 and 3)
Summary
Vertebrate embryonic development is characterized by three processes, cell proliferation, differentiation and migration. In vertebrates the earliest two processes conducted by cell migration are the formation of the three germ layers during gastrulation by epiboly and internalization (or ingression/emboly, depending on the organism), and the formation of the mediolateral body axis by convergence and extension (C/E) cell movements [1,2]. C/E cell movements require cells of the axial and paraxial mesoderm and neurectoderm to polarize and elongate in their direction of movement. These cells migrate towards the dorsal midline and participate in a process called intercalation in order to extend the body axis. Additional phenotypes of C/E defects constitute neural tube defects and cyclopia [1,3,4,5,6,7,8,9]
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