1. Title : SoxF-mediated vascular network formation

2. Speaker : Injune Kim (Associate Professor, Graduate School of Medical Science & Engineering, KAIST)

3. Date & Time : 16:30~17:45, September 20th (Wed)

4. Venue : #207, YBS BID(E16-1),KAIST

5. Abstract:

    We have been exploring multifaceted function of Sox7 and Sox17 belonging to SoxF subgroup in various vascular contexts. VEGF signaling is a key pathway for angiogenesis and requires highly coordinated regulation. Though the Notch pathway-mediated suppression of excessive VEGF activity via negative feedback is well known, the positive feedback control for augmenting VEGF signaling remains poorly understood. Sox7 and Sox17 are coincidently expressed and jointly promote developmental angiogenesis. VEGF signaling upregulates both Sox7 and Sox17 expression in angiogenesis, which then promote VEGFR2 expression, creating a positive feedback loop. Therefore, SoxF transcription factors act as positive feedback regulators reinforcing VEGF signaling and are indispensable players in developmental angiogenesis. On the contrary, Sox7 promotes tumor angiogenesis in high-grade glioma models by upregulating VEGFR2 whereas Sox17 inhibits it. Sox17 represses Sox7 expression in high-grade glioma vessels, indicating its epistatic regulation to Sox7 in tumor contexts. On the other hand, Sox17 is known to be critical for arterial development. Several GWAS analyses suggested Sox17 locus as one of candidate genomic region susceptible for intracranial aneurysm, a ballooning of intracerebral arteries. Sox17 is robustly expressed in arterial endothelial cells during adulthood and its deletion can induce intracranial aneurysm under hypertensive stress. We suggested Sox17 deficiency as a potential hereditary factor for intracranial aneurysm formation.