טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentYael Herzog
SubjectNeuropilins and their Role in Blood Vessel Development
DepartmentDepartment of Biology
Supervisor Professor Emeritus Neufeld Gera


Abstract

Neuropilins were discovered as receptors for axon guidance factors belonging to class-3 semaphorin subfamily. Neuropilins were subsequently found to function as receptors for vascular endothelial growth factor. We have cloned two chick isoforms of neuropilin-2 cDNA, and found that while neuropilin-1 is expressed preferentially in arteries, neuropilin-2 is preferentially expressed in veins. Using double in-situ hybridization experiments, we found that six somite embryos contain blood island subpopulations that express neuropilin-1 or neuropilin-2 as well as a subpopulation that co-expresses both neuropilins. In 13 somite embryos, the expression of neuropilin-1 and neuropilin-2 is segregated between the arterial and venous parts of the plexus despite the absence of blood flow. In 26 somite embryos, posterior blood islands expressing exclusively neuropilin-2 appear to undergo fusion to form the posterior sinus vein and its tributaries, suggesting that the venous identity of these veins may be established prior to their formation. Potential sites of semaphorin activity are expected to occur where neuropilins and plexins are co-expressed. Such sites were found in veins and in intra-embryonic arteries of 26 somite embryos, and in blood islands subpopulations of six somite embryos. Using a whole mount binding assay we found that semaphorin-3f bound exclusively to neuropilin-2 expressing cells regardless of the presence of plexin-A1 or plexin-A2. We have also found that semaphorin-3f inhibits sprouting from venous rings. Semaphorin-3f also inhibited sprouting from arterial rings, although less efficiently than from venous rings.