| Budget Amount *help |
¥49,790,000 (Direct Cost: ¥38,300,000、Indirect Cost: ¥11,490,000)
Fiscal Year 2007: ¥24,050,000 (Direct Cost: ¥18,500,000、Indirect Cost: ¥5,550,000)
Fiscal Year 2006: ¥25,740,000 (Direct Cost: ¥19,800,000、Indirect Cost: ¥5,940,000)
|
|---|
| Research Abstract |
A number of semaphorins have been shown to play crucial roles in the hard wiring of the nervous system, including fasciculation, axon branching, and target selection as axon guidance cues. However, increasing evidence has also attested to the significance of semaphorins in the development of other organ systems such as cardiovascular systems. Targeted disruptions of certain semaphorins or their receptors have been shown to results in various defects in the vascular system. Furthermore, several studies suggests that some semaphorins may contribute to the development of cardiovascular systems by controlling migration of endothelial cells, cardiac myocyte or their precursors. In this study, we have investigated the role of semaphorin in the cardiac outflow tract formation and angiogenesis.
(1) Semaphorin-plexin signaling in cardiac outflow tract formation
Some population of neural crest cells migrate into cardiac outflow tract and differentiate into the mesenchymal cells. We have found the up-regulation of Plexin-A2, neuropilins-1 and Plexin-D1 in migrating neural crest cells. Ligands, Sema6A and Sema6B, expressed in the dorsal side, repelled neural crest cell migration through Plexin-Al, and Sema3C, expressed in the cardiac outflow, attracted neural crest cells through neuropilins-1/plexin-D1 complex.
(2) Sema4A in angiogenesis
Sema4A-deficient mice exhibited the enhanced angiogenesis. We have found the this inhibitory effect on angiogenesis is mediated by the Sema4A-Plexin-D1 signaling.
|
