Dissertation And Wnt

Dissertation And Wnt-15
In study II, we investigated the expression of mammalian Wnts in developing choroid plexi.We discovered that biologically active Wnt5a is secreted to the cerebral spinal fluid (CSF) by the epithelial cells of the hindbrain, but not the telencephalic choroid plexus, in both mouse and in human embryos.

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Please find below the main highlights of each study included in this thesis.

In study I, we explored the molecular mechanism by which the crucial Wnt signaling integrator Dvl and the cell cycle protein kinase NEK2 regulate the progression of cells from the G2 to the M phase.

This thesis investigates the effects of altered Wnt/ PCP signaling during neurulation in mouse embryos, its importance in cell-cell adhesion and its role in pediatric cancer.

The developing central nervous system (CNS) comprises different patterning centers consisting of groups of cells with organizer-like properties.

Analysis of Wnt5a-/-, Wnt5a overexpressing, Wnt5a-/-; Ror2-/- and Ror2-/-; Vangl2-/- mice identified a function of the Wnt5a-Ror2/Vangl2 signaling axis in the VM morphogenesis and in m DA neuron development.

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Our study shows that correct Wnt5a expression levels are crucial for VM morphogenesis, m DA neurogenesis and m DA neuron maturation.

Moreover, we suggest that the pathogenesis of PD may involve an alteration in the balance between these two Wnt signaling pathways. Cervenka I, Valnohova J, Bernatik O, Harnos J, Radsetoulal M, Sedova K, Hanakova K, Potesil D, Sedlackova M, Salasova A, Steinhart Z, Angers S, Schulte G, Hampl A, Zdrahal Z, Bryja V. Fulltext (DOI) Pubmed View record in Web of Science® II.

Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins. Kaiser K, Gyllborg D, Salašová A, Molina FL, Laguna-Goya R, Potěšil D, Barker RA, Gato Casado Á, Bryja V, Arenas E, Villaescusa JC: WNT5A is transported via lipoprotein particles in the cerebrospinal fluid and regulates progenitor proliferation. Gyllborg D, Salašová A, Toledo EM, Gao B, Yang Y, Villaescusa JC, van Amerongen R, Arenas E: Ror2 and Vangl2 control dopaminergic neurogenesis and multiple aspects of cell polarity in the midbrain floor plate. Salašová A, Yokota C, Kasper Kjaer-Sorensen, Vestergaard B, Navis A, Thomasen P, Bernatik O, Varas M, Ernfors P, Bryja V, Nykjaer A, Arenas E: Proneurotrophin receptor Sor CS2 is a novel regulator of WNT/PCP pathway during embryogenesis. Salašová A, Yokota C, Potěšil D, Zdráhal Z, Bryja V, Arenas E.

A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway.

Wnt/Planar Cell Polarity (PCP) signaling is involved in many cellular processes throughout the development of the embryo.

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