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Cerebral Vein Malformations Result from Loss of Twist1 Expression and BMP Signaling from Skull Progenitor Cells and Dura.
Dev Cell 2017; 42(5):445-461.e5DC

Abstract

Dural cerebral veins (CV) are required for cerebrospinal fluid reabsorption and brain homeostasis, but mechanisms that regulate their growth and remodeling are unknown. We report molecular and cellular processes that regulate dural CV development in mammals and describe venous malformations in humans with craniosynostosis and TWIST1 mutations that are recapitulated in mouse models. Surprisingly, Twist1 is dispensable in endothelial cells but required for specification of osteoprogenitor cells that differentiate into preosteoblasts that produce bone morphogenetic proteins (BMPs). Inactivation of Bmp2 and Bmp4 in preosteoblasts and periosteal dura causes skull and CV malformations, similar to humans harboring TWIST1 mutations. Notably, arterial development appears normal, suggesting that morphogens from the skull and dura establish optimal venous networks independent from arterial influences. Collectively, our work establishes a paradigm whereby CV malformations result from primary or secondary loss of paracrine BMP signaling from preosteoblasts and dura, highlighting unique cellular interactions that influence tissue-specific angiogenesis in mammals.

Authors+Show Affiliations

Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA; FM Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: max.tischfield@gmail.com.Department of Radiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Radiology, Harvard Medical School, Boston, MA 02115, USA.Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA.Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA.Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA; FM Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA.Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA.Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA; FM Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.Department of Ophthalmology, Boston Children's Hospital, Boston, MA 02115, USA.Department of Ophthalmology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA.Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Ophthalmology, Boston Children's Hospital, Boston, MA 02115, USA; FM Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: elizabeth.engle@childrens.harvard.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28844842

Citation

Tischfield, Max A., et al. "Cerebral Vein Malformations Result From Loss of Twist1 Expression and BMP Signaling From Skull Progenitor Cells and Dura." Developmental Cell, vol. 42, no. 5, 2017, pp. 445-461.e5.
Tischfield MA, Robson CD, Gilette NM, et al. Cerebral Vein Malformations Result from Loss of Twist1 Expression and BMP Signaling from Skull Progenitor Cells and Dura. Dev Cell. 2017;42(5):445-461.e5.
Tischfield, M. A., Robson, C. D., Gilette, N. M., Chim, S. M., Sofela, F. A., DeLisle, M. M., ... Engle, E. C. (2017). Cerebral Vein Malformations Result from Loss of Twist1 Expression and BMP Signaling from Skull Progenitor Cells and Dura. Developmental Cell, 42(5), pp. 445-461.e5. doi:10.1016/j.devcel.2017.07.027.
Tischfield MA, et al. Cerebral Vein Malformations Result From Loss of Twist1 Expression and BMP Signaling From Skull Progenitor Cells and Dura. Dev Cell. 2017 09 11;42(5):445-461.e5. PubMed PMID: 28844842.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cerebral Vein Malformations Result from Loss of Twist1 Expression and BMP Signaling from Skull Progenitor Cells and Dura. AU - Tischfield,Max A, AU - Robson,Caroline D, AU - Gilette,Nicole M, AU - Chim,Shek Man, AU - Sofela,Folasade A, AU - DeLisle,Michelle M, AU - Gelber,Alon, AU - Barry,Brenda J, AU - MacKinnon,Sarah, AU - Dagi,Linda R, AU - Nathans,Jeremy, AU - Engle,Elizabeth C, Y1 - 2017/08/30/ PY - 2016/06/19/received PY - 2017/05/04/revised PY - 2017/07/31/accepted PY - 2017/8/29/pubmed PY - 2017/9/26/medline PY - 2017/8/29/entrez KW - BMP2 KW - BMP4 KW - ICP KW - Twist1 KW - cerebral veins KW - coronal suture KW - craniosynostosis KW - osteoblast KW - skull KW - venous angiogenesis SP - 445 EP - 461.e5 JF - Developmental cell JO - Dev. Cell VL - 42 IS - 5 N2 - Dural cerebral veins (CV) are required for cerebrospinal fluid reabsorption and brain homeostasis, but mechanisms that regulate their growth and remodeling are unknown. We report molecular and cellular processes that regulate dural CV development in mammals and describe venous malformations in humans with craniosynostosis and TWIST1 mutations that are recapitulated in mouse models. Surprisingly, Twist1 is dispensable in endothelial cells but required for specification of osteoprogenitor cells that differentiate into preosteoblasts that produce bone morphogenetic proteins (BMPs). Inactivation of Bmp2 and Bmp4 in preosteoblasts and periosteal dura causes skull and CV malformations, similar to humans harboring TWIST1 mutations. Notably, arterial development appears normal, suggesting that morphogens from the skull and dura establish optimal venous networks independent from arterial influences. Collectively, our work establishes a paradigm whereby CV malformations result from primary or secondary loss of paracrine BMP signaling from preosteoblasts and dura, highlighting unique cellular interactions that influence tissue-specific angiogenesis in mammals. SN - 1878-1551 UR - https://www.unboundmedicine.com/medline/citation/28844842/Cerebral_Vein_Malformations_Result_from_Loss_of_Twist1_Expression_and_BMP_Signaling_from_Skull_Progenitor_Cells_and_Dura_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1534-5807(17)30628-7 DB - PRIME DP - Unbound Medicine ER -