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a Hippo-Yap pathway in cranial bone development and regeneration

颅骨发育和再生中的 Hippo-Yap 通路

基本信息

批准号：
9385137
负责人：
Jun Wang
金额：
$ 14.79万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9385137
关键词：
Alleles Binding Sites Bioinformatics Bone Density Bone Development Bone Regeneration CRISPR/Cas technology Calvaria Candidate Disease Gene Cell Culture Techniques Cell Differentiation process Cell Nucleus Cell Proliferation Cells Cephalic DNA Binding Data Defect Embryo Environment Extracellular Matrix Future Gene Expression Gene Targeting Genes Goals Hydrogels In Vitro Joint structure of suture of skull Knock-out Ligands Mandible Mechanics Mediating Mediator of activation protein Mentored Research Scientist Development Award Methods Modeling Mus NOTCH3 gene Natural regeneration Neural Crest Nuclear Nucleic Acid Regulatory Sequences Organ Size Osteoblasts Osteogenesis Pathway interactions Phosphotransferases Physiologic Ossification Play Regenerative Medicine Regulator Genes Reporting Research Role Sampling Signal Pathway Signal Transduction Survivors System Testing Time Tissues Training bone craniofacial craniofacial development extracellular genome editing in vitro activity in vivo inhibitor/antagonist injured knock-down mechanical properties mouse model mutant notch protein novel postnatal receptor repaired response skeletal tool transcriptome sequencing

项目摘要

The role of the Hippo-signaling pathway, an evolutionarily conserved organ size control pathway, in cranial bone development and regeneration is poorly understood. We specifically inactivated the Hippo component Salv, and Hippo downstream effectors Yap and Taz in the cranial neural crest (CNC) using the Wnt1cre driver and Wnt1cre2SOR drivers. Salv conditional knock-out (CKO) mutants had dramatically enlarged calvarial bones and cranial sutures with increased calvarial bone density, whereas mutants of Taz homozygous and Yap heterozygous CKO had a range of survival times from E14.5 to postnatal 8 weeks with a range of calvarial bone defects with Wormian bones and decreased calvarial bone density. Notably, our preliminary data suggested that expression and subcellular localization of Yap changes upon Hippo kinase activity, extracellular matrix rigidity and Notch signaling activity. In this proposed K01 study, we investigate the function of Hippo signaling and Yap/Taz mediated signaling crosstalk during cranial bone development and regeneration and will study three aims: 1) To investigate the hypothesis that Hippo signaling and extracellular environment cooperatively regulate osteoblast proliferation and differentiation during cranial bone formation; 2) To investigate the signaling cross talk between Hippo and Notch signaling during cranial bone development; 3) To identify novel target genes of Hippo signaling during cranial bone development and regeneration. My research will focus on bone regeneration and treatment of severely injured bone. This K01 study will provide preliminary data and potential targets in bone regenerative medicine for my subsequent R01 application.

hippo信号通路的作用，一个进化保守的器官大小控制