The cardiovascular system is the first organ to become functional during vertebrate embryogenesis. We are studying the morphogenetic mechanisms, which underly the formation of intersomitic blood vessels (ISV). ISVs are arranged in a metameric pattern along the body axis and appear phenotypically identical to each other. However, at the cellular level, by labeling cell-cell junctions, two types of vascular architectures, unicellular and multicellular, can be distinguished - and it has been shown that these vessel types are formed by very different morphogenetic processes.

In order to find out, whether the initial vascular architectures are fixed or can be converted, we have followed fluorescent junctional reporters over several days of development.

Quantification of junctional patterns showed an increase of multicellular ISV at 72 hpf when compared to 48 hpf. Time-lapse analysis of individual ISV over 2 days of development revealed that (1) unicellular tubes transform into multicellular tubes by cell rearrangements; (2) multi-cellular tubes are stable in their architecture; (3) in rare cases endothelial cells deintercalated to form unicellular tubes with autocellular junctions.

These observations demonstrate an overall tendency of endothelial cells to form multicellular cellular tubes by cell rearrangement/intercalation. We are now investigating genetic components that may regulate this behavior. To this end we have generated mutants in zebrafish PI3 kinase genes (i.e. pik3c-aa and -ab), a pathway implicated in blood vessel formation and directed cell migration. We are currently investigating the consequences of loss of PI3 kinase function with respect to endothelial cell rearrangement and ISV architecture.