The Heart of Glass-Cerebral Cavernous Malformation (Heg-CCM) pathway is essential for normal cardiovascular development in zebrafish and mouse. In zebrafish, the Heg-CCM pathway mutants santa (ccm1/san), valentine (ccm2/vtn), and heart of glass (heg) exhibit severely dilated hearts and inflow tracts and a complete absence of blood circulation. We identified a novel gene based on its sequence identity with ccm2, which we have named ccm2-like (ccm2l), and characterized its role in cardiovascular development. Disruption of ccm2l by morpholino injection causes dilation of the atrium and inflow tract and compromised blood circulation. Morpholino co-injection experiments identify ccm2l as an enhancer of the characteristic Heg-CCM dilated heart phenotype, and we find that ccm2 overexpression can partially rescue ccm2l morphant defects. Finally, we show that Ccm2l binds Ccm1 and perform deletion and mutational analyses to define the regions of Ccm1 that mediate its binding to Ccm2l and its previously established interactors Ccm2 and Heg. These genetic and biochemical data argue that ccm2l is a necessary component of the Heg-CCM pathway. (C) 2013 Elsevier Inc. All rights reserved.
机构:
Hubrecht Inst, NL-3584 CT Utrecht, Netherlands
Univ Med Ctr Utrecht, NL-3584 CT Utrecht, NetherlandsNYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USA
Clijsters, Linda
Marques, Sara R.
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USA
Univ Porto, Grad Program Areas Basic & Appl Biol, P-4050465 Oporto, PortugalNYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USA
Marques, Sara R.
Lin, Yi-Fan
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USANYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USA
Lin, Yi-Fan
Garavito-Aguilar, Zayra V.
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USANYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USA
Garavito-Aguilar, Zayra V.
Yelon, Deborah
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USANYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USA
机构:
Hubrecht Inst, NL-3584 CT Utrecht, Netherlands
Univ Med Ctr Utrecht, NL-3584 CT Utrecht, NetherlandsNYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USA
Clijsters, Linda
Marques, Sara R.
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USA
Univ Porto, Grad Program Areas Basic & Appl Biol, P-4050465 Oporto, PortugalNYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USA
Marques, Sara R.
Lin, Yi-Fan
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USANYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USA
Lin, Yi-Fan
Garavito-Aguilar, Zayra V.
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USANYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USA
Garavito-Aguilar, Zayra V.
Yelon, Deborah
论文数: 0引用数: 0
h-index: 0
机构:
NYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USANYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr Biol & Med, New York, NY 10016 USA