@article{TEXTUAL,
      recid = {9933},
      author = {Li, Wenqing and Tran, Virginia and Shaked, Iftach and Xue,  Belinda and Moore, Thomas and Lightle, Rhonda and  Kleinfeld, David and Awad, Issam A. and Ginsberg, Mark H.},
      title = {Abortive intussusceptive angiogenesis causes  multi-cavernous vascular malformations},
      journal = {eLife},
      address = {2021-05-20},
      number = {TEXTUAL},
      abstract = {Mosaic inactivation of CCM2 in humans causes cerebral  cavernous malformations (CCMs) containing adjacent dilated  blood-filled multi-cavernous lesions. We used CRISPR-Cas9  mutagenesis to induce mosaic inactivation of zebrafish ccm2  resulting in a novel lethal multi-cavernous lesion in the  embryonic caudal venous plexus (CVP) caused by obstruction  of blood flow by intraluminal pillars. These pillars mimic  those that mediate intussusceptive angiogenesis; however,  in contrast to the normal process, the pillars failed to  fuse to split the pre-existing vessel in two. Abortive  intussusceptive angiogenesis stemmed from mosaic  inactivation of ccm2 leading to patchy klf2a overexpression  and resultant aberrant flow signaling. Surviving adult fish  manifested histologically typical hemorrhagic CCM.  Formation of mammalian CCM requires the flow-regulated  transcription factor KLF2; fish CCM and the embryonic CVP  lesion failed to form in klf2a null fish indicating a  common pathogenesis with the mammalian lesion. These  studies describe a zebrafish CCM model and establish a  mechanism that can explain the formation of characteristic  multi-cavernous lesions.},
      url = {http://knowledge.uchicago.edu/record/9933},
}