Leiden University Scholarly Publications

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Runtuwene, V.J. (2012)

Functional characterization of protein-tyrosine phosphatases in zebrafish development using image analysis.

Doctoral Thesis
During gastrulation, the cells, and consequently the organ anlagen, are repositioned according to their future arrangement along the anterio- posterior axis. The movements responsible, the convergence and extension (CE) cell movements, are crucial for normal development and defects in their mechanism underlie human pathologies like spina bifida and Noonan syndrome. Collective polarization of the cells is essential for these morphogenetic. The coordination and regulation are governed by intricate signaling mechanisms. Tyrosine phosphorylation is one of such mechanisms. By either phosphorylation by protein-tyrosine kinases or dephosphorylation by protein-tyrosine phosphatases (PTPs) of tyrosine residues, many signaling proteins can be switched from active to inactive states. In this thesis, we focus on the role of ‘classical’ PTPs. We identified PTP-BL, Ptpn20, RPTPα and RPTPε as components of a system regulating cell polarity. Additionally, we identified via screening one...Show moreDuring gastrulation, the cells, and consequently the organ anlagen, are repositioned according to their future arrangement along the anterio- posterior axis. The movements responsible, the convergence and extension (CE) cell movements, are crucial for normal development and defects in their mechanism underlie human pathologies like spina bifida and Noonan syndrome. Collective polarization of the cells is essential for these morphogenetic. The coordination and regulation are governed by intricate signaling mechanisms. Tyrosine phosphorylation is one of such mechanisms. By either phosphorylation by protein-tyrosine kinases or dephosphorylation by protein-tyrosine phosphatases (PTPs) of tyrosine residues, many signaling proteins can be switched from active to inactive states. In this thesis, we focus on the role of ‘classical’ PTPs. We identified PTP-BL, Ptpn20, RPTPα and RPTPε as components of a system regulating cell polarity. Additionally, we identified via screening one additional PTP, ptprda, as essential for CE movements. Quantitative analysis and clear representation of the data is essential to modern day biology. Studying collective cell migrations requires the analysis of the net effect of cell polarization and/or displacements of a large number of cells within a tissue rather than measurements of a few individuals. An automated cell tracing algorithm was developed and an algorithm for the detection of cell membranes. Additionally, a novel method of graphical data representation is introduced.Show less
Zebrafish
RhoA
Ptp
Morpholino
Image processing
Imaging
Gastrulation
Cell polarization
All authors
Runtuwene, V.J.
Supervisor
Hertog, J. den
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Science, Leiden University
Date
2012-09-12
ISBN (print)
9789461901347

Juridical information

Court
LEI Universiteit Leiden

Funding

Sponsorship
Marie Curie Research Training Network Grant