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... 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
The research described in this thesis mainly focussed on making and refining a model that describes axial patterning during gastrulation in the frog Xenopus laevis. Chapter 2 and 3 describe that... Show moreThe research described in this thesis mainly focussed on making and refining a model that describes axial patterning during gastrulation in the frog Xenopus laevis. Chapter 2 and 3 describe that axial information arises in the mesoderm and subsequently in the neurectoderm. Also is shown that this information, under influence of the Spemann organiser and cellular movements, is translated from a time sequence into a space sequence. The function of the Spemann organiser, important for AP patterning is neural induction. In chapter 4 is described that retinoids, important for axial patterning and formed in the mesoderm, have a patterning effect on neurectoderm. An important conclusion in this chapter is that retinoids are candidates for transfer of axial information from mesoderm to neurectoderm and can, in this way, coordinate the expression of axial information between mesoderm and neurectoderm. In chapter 5 a study is described where the transcriptional targets of Hoxc6 or Antennapedia in the frog Xenopus laevis and the fruitfly Drosophila melanogaster are compared. From this comparison conclusions can be drawn about the processes that are important for the function of Hoxc6/Antp. From this study could be concluded that celldivision, cellmigration, and suppresion of head formation are processes that are important for the function of Hoxc6/Antp. Show less
