Rapamycin rescues BMP mediated midline craniosynostosis phenotype through reduction of mTOR signaling in a mouse model

Kaitrin Kramer, Jingwen Yang, W. Benton Swanson, Satoru Hayano, Masako Toda, Haichun Pan, Jin Koo Kim, Paul H. Krebsbach, Yuji Mishina

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Craniosynostosis is defined as congenital premature fusion of one or more cranial sutures. While the genetic basis for about 30% of cases is known, the causative genes for the diverse presentations of the remainder of cases are unknown. The recently discovered cranial suture stem cell population affords an opportunity to identify early signaling pathways that contribute to craniosynostosis. We previously demonstrated that enhanced BMP signaling in neural crest cells (caA3 mutants) leads to premature cranial suture fusion resulting in midline craniosynostosis. Since enhanced mTOR signaling in neural crest cells leads to craniofacial bone lesions, we investigated the extent to which mTOR signaling is involved in the pathogenesis of BMP-mediated craniosynostosis by affecting the suture stem cell population. Our results demonstrate a loss of suture stem cells in the caA3 mutant mice by the newborn stage. We have found increased activation of mTOR signaling in caA3 mutant mice during embryonic stages, but not at the newborn stage. Our study demonstrated that inhibition of mTOR signaling via rapamycin in a time specific manner partially rescued the loss of the suture stem cell population. This study provides insight into how enhanced BMP signaling regulates suture stem cells via mTOR activation.

Original languageEnglish
Article numbere23220
JournalGenesis
Volume56
Issue number6-7
DOIs
Publication statusPublished - Jun 1 2018

Fingerprint

Craniosynostoses
Sirolimus
Cranial Sutures
Stem Cells
Sutures
Phenotype
Neural Crest
Population
Bone and Bones
Genes

Keywords

  • BMP Smad signaling
  • craniosynostosis
  • mTOR
  • neural crest cells
  • suture

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Cell Biology

Cite this

Rapamycin rescues BMP mediated midline craniosynostosis phenotype through reduction of mTOR signaling in a mouse model. / Kramer, Kaitrin; Yang, Jingwen; Swanson, W. Benton; Hayano, Satoru; Toda, Masako; Pan, Haichun; Kim, Jin Koo; Krebsbach, Paul H.; Mishina, Yuji.

In: Genesis, Vol. 56, No. 6-7, e23220, 01.06.2018.

Research output: Contribution to journalArticle

Kramer, K, Yang, J, Swanson, WB, Hayano, S, Toda, M, Pan, H, Kim, JK, Krebsbach, PH & Mishina, Y 2018, 'Rapamycin rescues BMP mediated midline craniosynostosis phenotype through reduction of mTOR signaling in a mouse model', Genesis, vol. 56, no. 6-7, e23220. https://doi.org/10.1002/dvg.23220
Kramer, Kaitrin ; Yang, Jingwen ; Swanson, W. Benton ; Hayano, Satoru ; Toda, Masako ; Pan, Haichun ; Kim, Jin Koo ; Krebsbach, Paul H. ; Mishina, Yuji. / Rapamycin rescues BMP mediated midline craniosynostosis phenotype through reduction of mTOR signaling in a mouse model. In: Genesis. 2018 ; Vol. 56, No. 6-7.
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