UTR untranslated region WHIM syndrome wart, hypogammaglobulinemia, infection, and myelokathexis syndrome Cell migration in multicellular organisms and the role of ECM Although research on migrating unicellular organisms such as Dictyostelium has given a lot of insight into cell migration processes these model systems lack an important aspect of cell migration in the higher eukaryotes: in complex tissues and organs cells encounter many different cell types and signals at the same time [49] [50]

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... 51] . Although Dictyostelium can assemble into multicellular structures, these are not comparable to the highly developed tissues found in vertebrate animals. Here a multitude of cells and different tissue types have assembled to form functional organs. In addition to cells, the extracellular matrix (ECM), a large repertoire of extracellular proteins and sugar chains to which cells adhere, provides three-dimensional structure and support to these organs 52, 53 . The ECM proteins are often modified with glycosaminoglycans (GAG), highly charged, and crosslinked, either directly through chemical modifications or by linker proteins 54 . Depending on composition of GAGs, types of modifications and the presence of linker proteins, unique ECM properties and functions are established, thereby characterizing the function of the tissues 55, 56 . Chemokines Belonging to the group of cytokines, chemokines (chemotactic cytokines) represent one of the most important families of chemotactic molecules 84, 85 . Initially found to be important chemoattractants for lymphocytes 86 , today it has been acknowledged that chemokines have numerous functions in development [87] [88] [89] , homeostasis 72, 90 , and disease 22, 91, 92 . Chemokine receptors have also been shown to activate the phosphatidylinositol-3-kinase (PI3K) pathway 125 . PI3K is involved in many directional migration processes by creating an intracellular gradient of phosphatidyl-3,4,5-trisphosphate (PIP 3 ) 126 . PIP3 is not only an important activator of the Akt/protein kinase B (Akt/PKB) pathway, but also many cytoskeletal components have PIP3-binding Pleckstrin homology domains (PH-the time of inflammation. Loss of D6 in turn causes massive inflammation, which leads to severe tissue damage 169, 170 . Decoy receptors have also been implied to mediate transcytosis and subsequent presentation of chemokines to the blood stream by endothelial cells, thereby allowing an immune defense to take place 171, 172 . Not all decoy receptors are silent. When required some chemokine receptors can switch from a signaling to a Primordial germ cell migration This work focuses on mechanisms that control directional migration of primordial germ cells (PGCs). PGCs are the earliest progenitors of the gametes that will form sperm and egg 185, 186 . Specification of PGCs differs between species and is carried out either by the deposition of maternal determinants (C. elegans, Drosophila, Xenopus, zebrafish, chicken) or through inductive signals from neighboring cells (Urodele amphibians,