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SUMMARY:BMP9 and BMP10\, two new key players in blood and lymphatic vascul
 ar development
DTSTART:20150824T133000
DTEND:20150824T143000
DTSTAMP:20260916T225837Z
UID:5f3c3ddf1fbf09d49f46448c4b30c1ed1f7feb39f604cf93dbecacd6
CATEGORIES:Conferences - Seminars
DESCRIPTION:Sabine Bailly\nLaboratoire de Biologie du Cancer et de l’Inf
 ection\, INSERM U1036-CEA-Grenoble/Université Grenoble-Alpes\nBMP9 (Bone 
 Morphogenetic Proteins) and BMP10 are two members of the TGFß superfamily
 . In 2007\, our team demonstrated that they bind with high affinity to the
  receptor ALK1 (activin receptor-like kinase 1)\, a receptor specifically 
 expressed on blood and lymphatic endothelial cells1 that plays a key role 
 in vascular development.\nBMP9 and BMP10 are both present in blood and\, w
 e have recently shown that they play critical and specific roles in blood 
 and lymphatic development. Using Bmp9 knockout mice\, we found that Bmp9 i
 nactivation had no significant effect on blood vascularization of mouse re
 tina\, however addition of a neutralizing anti-BMP10 antibody strongly aff
 ected retinal vascularization (inhibition of vascular radial expansion and
  increase in vessel density) in Bmp9 knockout mice but not in WT mice2\, d
 emonstrating that BMP9 and BMP10 play a redundant role in retinal vascular
 ization. We also found that they play a redundant role in vascular remodel
 ing of larger vessels such as the ductus arteriosus\, which plays a key ro
 le at birth allowing pulmonary circulation3. On the other hand\, Bmp9 knoc
 kout mice were defective in lymphatic valve formation and lymphatic matura
 tion4\, demonstrating a specific role for BMP9 in lymphatic development. B
 MP9 and BMP10 are also associated to vascular diseases. Indeed\, we could 
 show that some mutations in ALK1 or its co-receptor endoglin identified in
  HHT (hemorrhagic hereditary telangiectasia) patients can lead to a defect
  in BMP9 or BMP10 binding5\, 6. We were also able to propose that an anti-
 angiogenic treatment could be beneficial to HHT patients7.\nTaken together
 \, these results clearly demonstrate that the BMP9/BMP10/ALK1 is an emergi
 ng vascular signaling pathway with potential therapeutic applications. A b
 etter understanding of the respective roles of these two BMPs is thus stro
 ngly needed in order to bring some new therapeutic approaches in the treat
 ment of vascular diseases but also in tumor angiogenesis and lymphangiogen
 esis.\n1. David L\, et al. Blood. 2007\;109:1953-1961\n2. Ricard N\, et al
 . Blood. 2012\;119:6162-6171\n3. Levet S\, et al. PNAS 2015\;112:E3207-321
 5\n4. Levet S\, et al. Blood. 2013\;122:598-607\n5. Ricard N\, et al. Bloo
 d. 2010\;116:1604-1612\n6. Mallet C\, et al. Hum Mol Genet. 2015\;24:1142-
 1154\n7. Dupuis-Girod S\, et al. JAMA. 2012\;307:948-955
LOCATION:SV1717.1 http://plan.epfl.ch/?room=SV%201717.1
STATUS:CONFIRMED
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