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Moreover, we found a novel phenotype of bilateral asymmetry in Ror2-/-; Vangl2-/- animals which suggests that Vangl2 alone or in a complex with Ror2 controls the correct position, proliferation and differentiation of m DA progenitors into m DA neuroblasts and neurons.
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.
In study V, we investigated whether Leucine-rich repeat kinase 2 (Lrrk2), the protein product of the park8 gene, which is mutated in more than 40% of patients with inherited PD, can interact with the Wnt/PCP pathway by using a proteomic screening.
We describe that Lrrk2 interacts with a number of Wnt/PCP components in dopaminergic cells, in the VM of E18.5 mice embryos, and in a human cell line.
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.
Wnt signaling controls a wide spectrum of complex cell responses during prenatal development, in the adulthood and during disease.
In this doctoral study, we have identified and explored novel regulatory components of Wnt/Planar Cell Polarity (PCP) pathway and their function in various cellular processes during embryogenesis and central nervous system (CNS) development.
We paid special attention to molecular mechanisms underlying the morphogenesis of the ventral midbrain (VM) and development of midbrain dopaminergic (m DA) neurons, a brain area that is strictly regulated by Wnt signaling.
We also touched upon possible clinical applications of our findings in neurodegenerative disorders, such as Parkinson's disease (PD).