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Functions of P38 and ERK kinases in zebrafish early development

Promotor: Prof.dr. H.P. Spaink, Co-promotor: Dr. B.E. Snaar

H. Rian
15 januari 2014
Thesis in Leiden Repository

Cells communicate in multicellular organisms; by secreting and sensing signals, in order to adjust their behavior to the environment. Extracellular signals such as cytokines and growth factors bind to cell surface receptors and trigger the activation of multiple protein signal transduction cascades that mediate cellular responses such as proliferation, differentiation, apoptosis and motility. The Mitogen-activated protein kinase (MAPK) family is a group of homologous proteins forming several linear signal transduction pathways. The MAPK family is conserved among eukaryotes and most vertebrates contain at least 14 MAPKs. We are interested in the molecular mechanisms of MAPK signalling that facilitate proper development of the zebrafish embryo. The zebrafish is an excellent model to delineate MAPK associated embryonic processes. The bodyplan is completed within 24hours and within a week most organs are formed. With the current available zebrafish tools molecular mechanisms could be identified and linked to cellular processes and morphological observations. We constructed constitutive active zebrafish Erk2 mutants for identification of new signalling events. We completed expression analysis of all P38 isoforms by expression analysis of the P38β and P38δ isoforms. We also performed a comparative study between P38α and Erk2 MAPK in gastrulation. Finally, We addressed the role of P38α in zebrafish angiogenesis.

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